AVAHO

Adding platinum-based chemotherapy to osimertinib (Tagrisso) in the first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC) improved progression-free survival (PFS), according to interim results from the FLAURA2 trial.

Combining the third-generation tyrosine kinase inhibitor (TKI) with platinum-based chemotherapy achieved “statistically significant and clinically meaningful improvement in PFS over osimertinib monotherapy,” said Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, both in Boston, who presented the interim findings at the annual World Conference on Lung Cancer.

However, experts raised some questions about whether the combination would also offer improved overall survival and whether the accompanying toxicity would be acceptable to patients.

Yi-Long Wu, MD, PhD, who was not involved in the research, said that although the combination regimen does appear to offer a benefit, it may come at a steep cost.

Patients who received the combination had an almost fourfold greater risk of grade 3 or higher adverse events related to treatment, said Dr. Wu, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.

And, notably, because the overall survival data in the interim analysis are immature, it’s unclear whether the combination will offer an overall survival benefit over osimertinib monotherapy, Dr. Wu said.

The 2019 FLAURA trial, which compared TKI monotherapy, demonstrated an overall survival advantage among patients who received osimertinib vs. a first-generation EGFR TKI, such as gefitinib (Iressa) or erlotinib (Tarceva). These data established the third-generation TKI as the preferred first-line treatment for patients with advanced EGFR NSCLC.

But resistance to EGFR TKIs remains a problem, which has led experts to explore combination strategies that might overcome resistance and improve clinical outcomes. Recent data indicate that combining first-generation EGFR TKIs with chemotherapy may have an additive effect and further improve outcomes with the drugs. And a recent study of untreated EGFR-mutated advanced NSCLC found patients receiving osimertinib plus platinum-pemetrexed demonstrated a promising objective response rate; however, Dr. Jänne noted that the combination has not been tested in a randomized trial.

To better understand the potential additive benefit of osimertinib and chemotherapy, the team conduced a global, open-label study in patients with pathologically confirmed nonsquamous NSCLC who had received no prior systemic therapy for advanced NSCLC and had a performance status of 0 or 1.

The team randomly assigned 557 patients to daily osimertinib alone or osimertinib plus chemotherapy with pemetrexed and carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed every 3 weeks.

Treatment was continued until radiological disease progression, as defined using the RECIST 1.1 criteria, or other withdrawal criteria were met. The patients were assessed at weeks 6 and 12, and again every 12 weeks.

The median age of the patients was about 61 years, approximately 61% were female, and about 25% were Asian. Around two-thirds were never-smokers, about 60% had either Ex19del or L858R EGFR mutations, and about 40% had central nervous system metastases.

At the data cutoff, the median follow-up was 16.5 months in the osimertinib monotherapy arm and 19.5 months in the combination arm. Overall, 45% of patients on monotherapy and 56% in the combination arm were still on treatment.

Dr. Jänne reported that osimertinib plus chemotherapy was associated with a greater objective response rate than monotherapy – 83.2% vs. 75.5% – and a longer median duration of response – 24 months vs. 15.3 months.

Patients receiving the combination showed significant improvements in PFS – 25.5 months vs. 16.7 months (hazard ratio, 0.62; P < .0001). At 24 months, 57% of the patients in the combination arm were disease-free vs. 41% in the monotherapy group.

The benefit held across all patient subgroups, including age, sex, smoking history, and EGFR mutation type at baseline.

The PFS benefit appeared most pronounced among patients with CNS metastases at baseline – a median of 24.9 months in the combination arm vs. 13.8 months with monotherapy (HR, 0.47). But patients without CNS metastases who received the combination therapy also showed improvements in PFS (HR, 0.75).

Should there be an overall survival improvement, then the regimen used in FLAURA2 could become the “new standard of care in EGFR-mutated NSCLC in the first-line setting,” particularly in patients with CNS metastases and/or an exon21 mutation, Dr. Wu said. If, however, further analysis indicates no overall survival benefit, then patients will have experienced chemotherapy side effects earlier and longer than those receiving monotherapy, with no life gain.

Dr. Wu pointed out that the future role and sequence of the combination will also hinge on understanding how patients become resistant to it as well as whether the toxicity is manageable.

The FLAURA2 safety data indicated that the combination led to higher rates of grade 3 or higher adverse events overall – 64% vs. 27% – and higher rates of grade 3 or higher adverse events possibly related to treatment – 53% vs. 11%.

Experts who commented on the study findings via X (formerly Twitter) echoed Dr. Wu’s sentiments about the study findings and implications.

Mohana Roy, MD, said she did not find the results surprising, given that “many of us are adding chemo on slow progression on osimertinib already,” but noted that “questions of sequencing” remain.

Christian Rolfo, MD, PhD, MBA, commented that questions about the “real benefit” of osimertinib plus chemotherapy in subgroups and degree of resistance remain. Further toxicity and overall survival data “will clarify the future of the combination,” said Dr. Rolfo, of Icahn School of Medicine at Mount Sinai, New York.

The study was funded by AstraZeneca. Dr. Jänne declared relationships with Gatekeeper Pharmaceuticals, Labcorp, Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Revolution Medicines, Takeda Oncology, Biocartis, Mirati Therapeutics, Transcenta, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Eisai, Ignyta, Novartis, Nuvalent, Pfizer, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, and Voronoi.

A version of this article first appeared on Medscape.com.

Adding platinum-based chemotherapy to osimertinib (Tagrisso) in the first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC) improved progression-free survival (PFS), according to interim results from the FLAURA2 trial.

Combining the third-generation tyrosine kinase inhibitor (TKI) with platinum-based chemotherapy achieved “statistically significant and clinically meaningful improvement in PFS over osimertinib monotherapy,” said Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, both in Boston, who presented the interim findings at the annual World Conference on Lung Cancer.

However, experts raised some questions about whether the combination would also offer improved overall survival and whether the accompanying toxicity would be acceptable to patients.

Yi-Long Wu, MD, PhD, who was not involved in the research, said that although the combination regimen does appear to offer a benefit, it may come at a steep cost.

Patients who received the combination had an almost fourfold greater risk of grade 3 or higher adverse events related to treatment, said Dr. Wu, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.

And, notably, because the overall survival data in the interim analysis are immature, it’s unclear whether the combination will offer an overall survival benefit over osimertinib monotherapy, Dr. Wu said.

The 2019 FLAURA trial, which compared TKI monotherapy, demonstrated an overall survival advantage among patients who received osimertinib vs. a first-generation EGFR TKI, such as gefitinib (Iressa) or erlotinib (Tarceva). These data established the third-generation TKI as the preferred first-line treatment for patients with advanced EGFR NSCLC.

But resistance to EGFR TKIs remains a problem, which has led experts to explore combination strategies that might overcome resistance and improve clinical outcomes. Recent data indicate that combining first-generation EGFR TKIs with chemotherapy may have an additive effect and further improve outcomes with the drugs. And a recent study of untreated EGFR-mutated advanced NSCLC found patients receiving osimertinib plus platinum-pemetrexed demonstrated a promising objective response rate; however, Dr. Jänne noted that the combination has not been tested in a randomized trial.

To better understand the potential additive benefit of osimertinib and chemotherapy, the team conduced a global, open-label study in patients with pathologically confirmed nonsquamous NSCLC who had received no prior systemic therapy for advanced NSCLC and had a performance status of 0 or 1.

The team randomly assigned 557 patients to daily osimertinib alone or osimertinib plus chemotherapy with pemetrexed and carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed every 3 weeks.

Treatment was continued until radiological disease progression, as defined using the RECIST 1.1 criteria, or other withdrawal criteria were met. The patients were assessed at weeks 6 and 12, and again every 12 weeks.

The median age of the patients was about 61 years, approximately 61% were female, and about 25% were Asian. Around two-thirds were never-smokers, about 60% had either Ex19del or L858R EGFR mutations, and about 40% had central nervous system metastases.

At the data cutoff, the median follow-up was 16.5 months in the osimertinib monotherapy arm and 19.5 months in the combination arm. Overall, 45% of patients on monotherapy and 56% in the combination arm were still on treatment.

Dr. Jänne reported that osimertinib plus chemotherapy was associated with a greater objective response rate than monotherapy – 83.2% vs. 75.5% – and a longer median duration of response – 24 months vs. 15.3 months.

Patients receiving the combination showed significant improvements in PFS – 25.5 months vs. 16.7 months (hazard ratio, 0.62; P < .0001). At 24 months, 57% of the patients in the combination arm were disease-free vs. 41% in the monotherapy group.

The benefit held across all patient subgroups, including age, sex, smoking history, and EGFR mutation type at baseline.

The PFS benefit appeared most pronounced among patients with CNS metastases at baseline – a median of 24.9 months in the combination arm vs. 13.8 months with monotherapy (HR, 0.47). But patients without CNS metastases who received the combination therapy also showed improvements in PFS (HR, 0.75).

Should there be an overall survival improvement, then the regimen used in FLAURA2 could become the “new standard of care in EGFR-mutated NSCLC in the first-line setting,” particularly in patients with CNS metastases and/or an exon21 mutation, Dr. Wu said. If, however, further analysis indicates no overall survival benefit, then patients will have experienced chemotherapy side effects earlier and longer than those receiving monotherapy, with no life gain.

Dr. Wu pointed out that the future role and sequence of the combination will also hinge on understanding how patients become resistant to it as well as whether the toxicity is manageable.

The FLAURA2 safety data indicated that the combination led to higher rates of grade 3 or higher adverse events overall – 64% vs. 27% – and higher rates of grade 3 or higher adverse events possibly related to treatment – 53% vs. 11%.

Experts who commented on the study findings via X (formerly Twitter) echoed Dr. Wu’s sentiments about the study findings and implications.

Mohana Roy, MD, said she did not find the results surprising, given that “many of us are adding chemo on slow progression on osimertinib already,” but noted that “questions of sequencing” remain.

Christian Rolfo, MD, PhD, MBA, commented that questions about the “real benefit” of osimertinib plus chemotherapy in subgroups and degree of resistance remain. Further toxicity and overall survival data “will clarify the future of the combination,” said Dr. Rolfo, of Icahn School of Medicine at Mount Sinai, New York.

The study was funded by AstraZeneca. Dr. Jänne declared relationships with Gatekeeper Pharmaceuticals, Labcorp, Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Revolution Medicines, Takeda Oncology, Biocartis, Mirati Therapeutics, Transcenta, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Eisai, Ignyta, Novartis, Nuvalent, Pfizer, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, and Voronoi.

A version of this article first appeared on Medscape.com.

Adding platinum-based chemotherapy to osimertinib (Tagrisso) in the first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC) improved progression-free survival (PFS), according to interim results from the FLAURA2 trial.

Combining the third-generation tyrosine kinase inhibitor (TKI) with platinum-based chemotherapy achieved “statistically significant and clinically meaningful improvement in PFS over osimertinib monotherapy,” said Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, both in Boston, who presented the interim findings at the annual World Conference on Lung Cancer.

However, experts raised some questions about whether the combination would also offer improved overall survival and whether the accompanying toxicity would be acceptable to patients.

Yi-Long Wu, MD, PhD, who was not involved in the research, said that although the combination regimen does appear to offer a benefit, it may come at a steep cost.

Patients who received the combination had an almost fourfold greater risk of grade 3 or higher adverse events related to treatment, said Dr. Wu, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.

And, notably, because the overall survival data in the interim analysis are immature, it’s unclear whether the combination will offer an overall survival benefit over osimertinib monotherapy, Dr. Wu said.

The 2019 FLAURA trial, which compared TKI monotherapy, demonstrated an overall survival advantage among patients who received osimertinib vs. a first-generation EGFR TKI, such as gefitinib (Iressa) or erlotinib (Tarceva). These data established the third-generation TKI as the preferred first-line treatment for patients with advanced EGFR NSCLC.

But resistance to EGFR TKIs remains a problem, which has led experts to explore combination strategies that might overcome resistance and improve clinical outcomes. Recent data indicate that combining first-generation EGFR TKIs with chemotherapy may have an additive effect and further improve outcomes with the drugs. And a recent study of untreated EGFR-mutated advanced NSCLC found patients receiving osimertinib plus platinum-pemetrexed demonstrated a promising objective response rate; however, Dr. Jänne noted that the combination has not been tested in a randomized trial.

To better understand the potential additive benefit of osimertinib and chemotherapy, the team conduced a global, open-label study in patients with pathologically confirmed nonsquamous NSCLC who had received no prior systemic therapy for advanced NSCLC and had a performance status of 0 or 1.

The team randomly assigned 557 patients to daily osimertinib alone or osimertinib plus chemotherapy with pemetrexed and carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed every 3 weeks.

Treatment was continued until radiological disease progression, as defined using the RECIST 1.1 criteria, or other withdrawal criteria were met. The patients were assessed at weeks 6 and 12, and again every 12 weeks.

The median age of the patients was about 61 years, approximately 61% were female, and about 25% were Asian. Around two-thirds were never-smokers, about 60% had either Ex19del or L858R EGFR mutations, and about 40% had central nervous system metastases.

At the data cutoff, the median follow-up was 16.5 months in the osimertinib monotherapy arm and 19.5 months in the combination arm. Overall, 45% of patients on monotherapy and 56% in the combination arm were still on treatment.

Dr. Jänne reported that osimertinib plus chemotherapy was associated with a greater objective response rate than monotherapy – 83.2% vs. 75.5% – and a longer median duration of response – 24 months vs. 15.3 months.

Patients receiving the combination showed significant improvements in PFS – 25.5 months vs. 16.7 months (hazard ratio, 0.62; P < .0001). At 24 months, 57% of the patients in the combination arm were disease-free vs. 41% in the monotherapy group.

The benefit held across all patient subgroups, including age, sex, smoking history, and EGFR mutation type at baseline.

The PFS benefit appeared most pronounced among patients with CNS metastases at baseline – a median of 24.9 months in the combination arm vs. 13.8 months with monotherapy (HR, 0.47). But patients without CNS metastases who received the combination therapy also showed improvements in PFS (HR, 0.75).

Should there be an overall survival improvement, then the regimen used in FLAURA2 could become the “new standard of care in EGFR-mutated NSCLC in the first-line setting,” particularly in patients with CNS metastases and/or an exon21 mutation, Dr. Wu said. If, however, further analysis indicates no overall survival benefit, then patients will have experienced chemotherapy side effects earlier and longer than those receiving monotherapy, with no life gain.

Dr. Wu pointed out that the future role and sequence of the combination will also hinge on understanding how patients become resistant to it as well as whether the toxicity is manageable.

The FLAURA2 safety data indicated that the combination led to higher rates of grade 3 or higher adverse events overall – 64% vs. 27% – and higher rates of grade 3 or higher adverse events possibly related to treatment – 53% vs. 11%.

Experts who commented on the study findings via X (formerly Twitter) echoed Dr. Wu’s sentiments about the study findings and implications.

Mohana Roy, MD, said she did not find the results surprising, given that “many of us are adding chemo on slow progression on osimertinib already,” but noted that “questions of sequencing” remain.

Christian Rolfo, MD, PhD, MBA, commented that questions about the “real benefit” of osimertinib plus chemotherapy in subgroups and degree of resistance remain. Further toxicity and overall survival data “will clarify the future of the combination,” said Dr. Rolfo, of Icahn School of Medicine at Mount Sinai, New York.

The study was funded by AstraZeneca. Dr. Jänne declared relationships with Gatekeeper Pharmaceuticals, Labcorp, Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Revolution Medicines, Takeda Oncology, Biocartis, Mirati Therapeutics, Transcenta, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Eisai, Ignyta, Novartis, Nuvalent, Pfizer, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, and Voronoi.

A version of this article first appeared on Medscape.com.

INTRODUCTION

Lymphadenopathy in Chronic Lymphocytic Leukemia (CLL) is a very common feature. However, sudden increase in lymphadenopathy or other symptoms like weight loss should be evaluated for possible metastatic malignancy. We describe a CLL patient with diffuse mediastinal lymphadenopathy who was diagnosed with metastatic bladder cancer without a primary bladder tumor mass on imaging.

CASE DESCRIPTION

A 60-year-old man with a 60 pack-year smoking history, alcoholic cirrhosis, and a 5-year history of stage 1 CLL presented with 3 months of progressive shortness of breath; persistent cough; chills; hemoptysis; and a steady weight loss of 35 lbs. Notably, he had no bladder symptoms. Initial labs showed leukocytosis of 35.8k with a lymphocytic predominance. Screening low-dose chest CT was positive for diffuse mediastinal lymphadenopathy. Subsequent PET/CT revealed numerous hypermetabolic lymph nodes in the neck, mediastinum, left hilum, and right periaortic abdominal region. CT Chest, Abdomen, Pelvis revealed progressive lymphadenopathy as seen in prior imaging, stable pulmonary nodules up to 4 mm in size, and splenomegaly. No distant primary sites, including of the bladder, were identified. Mediastinal lymph node biopsy confirmed metastatic poorly differentiated carcinoma with immunohistochemical staining negative for p40, p63, CK20, TTF-1, Napsin A, CDX2, CA19- 9, Calretinin, and D2-40 and positive for CK7, GATA3, Ber-EP4, and Uroplakin, supporting bladder as primary origin. Urology deferred a cystoscopy given his lack of urinary symptoms and positive biopsy and was started on Carboplatin/Gemcitabine for his metastatic disease. He was ineligible for Cisplatin given his cirrhosis and hearing impairment.

DISCUSSION

In patients with CLL, new onset mediastinal lymphadenopathy is concerning for disease progression and possible transformation to a diffuse b-cell lymphoma. However, this symptom has a broad differential, including primary lung carcinomas, sarcomas, and metastatic disease. While our patient’s PET/CT and pan-CT failed to identify a distant primary site, maintaining a low clinical suspicion for metastatic disease and doing a thorough work-up was paramount. Only through immunohistochemical staining were we able to diagnosis this patient with urothelial carcinoma.

CONCLUSIONS

Biopsy with immunohistochemical staining and maintaining a low suspicion for worsening lymphadenopathy can identify unusually presenting urothelial carcinomas in CLL patients.

INTRODUCTION

Lymphadenopathy in Chronic Lymphocytic Leukemia (CLL) is a very common feature. However, sudden increase in lymphadenopathy or other symptoms like weight loss should be evaluated for possible metastatic malignancy. We describe a CLL patient with diffuse mediastinal lymphadenopathy who was diagnosed with metastatic bladder cancer without a primary bladder tumor mass on imaging.

CASE DESCRIPTION

A 60-year-old man with a 60 pack-year smoking history, alcoholic cirrhosis, and a 5-year history of stage 1 CLL presented with 3 months of progressive shortness of breath; persistent cough; chills; hemoptysis; and a steady weight loss of 35 lbs. Notably, he had no bladder symptoms. Initial labs showed leukocytosis of 35.8k with a lymphocytic predominance. Screening low-dose chest CT was positive for diffuse mediastinal lymphadenopathy. Subsequent PET/CT revealed numerous hypermetabolic lymph nodes in the neck, mediastinum, left hilum, and right periaortic abdominal region. CT Chest, Abdomen, Pelvis revealed progressive lymphadenopathy as seen in prior imaging, stable pulmonary nodules up to 4 mm in size, and splenomegaly. No distant primary sites, including of the bladder, were identified. Mediastinal lymph node biopsy confirmed metastatic poorly differentiated carcinoma with immunohistochemical staining negative for p40, p63, CK20, TTF-1, Napsin A, CDX2, CA19- 9, Calretinin, and D2-40 and positive for CK7, GATA3, Ber-EP4, and Uroplakin, supporting bladder as primary origin. Urology deferred a cystoscopy given his lack of urinary symptoms and positive biopsy and was started on Carboplatin/Gemcitabine for his metastatic disease. He was ineligible for Cisplatin given his cirrhosis and hearing impairment.

DISCUSSION

In patients with CLL, new onset mediastinal lymphadenopathy is concerning for disease progression and possible transformation to a diffuse b-cell lymphoma. However, this symptom has a broad differential, including primary lung carcinomas, sarcomas, and metastatic disease. While our patient’s PET/CT and pan-CT failed to identify a distant primary site, maintaining a low clinical suspicion for metastatic disease and doing a thorough work-up was paramount. Only through immunohistochemical staining were we able to diagnosis this patient with urothelial carcinoma.

CONCLUSIONS

Biopsy with immunohistochemical staining and maintaining a low suspicion for worsening lymphadenopathy can identify unusually presenting urothelial carcinomas in CLL patients.

INTRODUCTION

Lymphadenopathy in Chronic Lymphocytic Leukemia (CLL) is a very common feature. However, sudden increase in lymphadenopathy or other symptoms like weight loss should be evaluated for possible metastatic malignancy. We describe a CLL patient with diffuse mediastinal lymphadenopathy who was diagnosed with metastatic bladder cancer without a primary bladder tumor mass on imaging.

CASE DESCRIPTION

A 60-year-old man with a 60 pack-year smoking history, alcoholic cirrhosis, and a 5-year history of stage 1 CLL presented with 3 months of progressive shortness of breath; persistent cough; chills; hemoptysis; and a steady weight loss of 35 lbs. Notably, he had no bladder symptoms. Initial labs showed leukocytosis of 35.8k with a lymphocytic predominance. Screening low-dose chest CT was positive for diffuse mediastinal lymphadenopathy. Subsequent PET/CT revealed numerous hypermetabolic lymph nodes in the neck, mediastinum, left hilum, and right periaortic abdominal region. CT Chest, Abdomen, Pelvis revealed progressive lymphadenopathy as seen in prior imaging, stable pulmonary nodules up to 4 mm in size, and splenomegaly. No distant primary sites, including of the bladder, were identified. Mediastinal lymph node biopsy confirmed metastatic poorly differentiated carcinoma with immunohistochemical staining negative for p40, p63, CK20, TTF-1, Napsin A, CDX2, CA19- 9, Calretinin, and D2-40 and positive for CK7, GATA3, Ber-EP4, and Uroplakin, supporting bladder as primary origin. Urology deferred a cystoscopy given his lack of urinary symptoms and positive biopsy and was started on Carboplatin/Gemcitabine for his metastatic disease. He was ineligible for Cisplatin given his cirrhosis and hearing impairment.

DISCUSSION

In patients with CLL, new onset mediastinal lymphadenopathy is concerning for disease progression and possible transformation to a diffuse b-cell lymphoma. However, this symptom has a broad differential, including primary lung carcinomas, sarcomas, and metastatic disease. While our patient’s PET/CT and pan-CT failed to identify a distant primary site, maintaining a low clinical suspicion for metastatic disease and doing a thorough work-up was paramount. Only through immunohistochemical staining were we able to diagnosis this patient with urothelial carcinoma.

CONCLUSIONS

Biopsy with immunohistochemical staining and maintaining a low suspicion for worsening lymphadenopathy can identify unusually presenting urothelial carcinomas in CLL patients.

FROM SOHO 2023

It may be possible for patients with Hodgkin lymphoma to safely skip their interim PET-CT scan (PET2) following two cycles of frontline brentuximab vedotin (Adcetris), according to research presented at the annual meeting of the Society of Hematologic Oncology in Houston.

Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda (Calif.) University Medical Center.

These studies, including one conducted by Dr. Samaeekia’s team, provide “evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin,” Dr. Samaeekia, who presented the data, concluded.

Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.

However, “there are obviously challenges associated with implementing a PET-guided approach,” said Dr. Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients’ risk for toxicities when treatment is escalated based on the scan results.

Given these caveats, Dr. Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.

Dr. Samaeekia’s team analyzed findings from three trials – ECHELON-1, AHOD1331, and BREACH – which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.

In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2 negative (94.9% vs. 90.6%; hazard ratio for death, 0.54) as well as those who were PET2 positive (95% vs. 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.

In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab – 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab “eliminated the predictive value of the interim PET assessment.” The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.

Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Dr. Samaeekia and colleagues found that 24 were PET2 negative and 12 were PET2 positive. All patients who were PET2 negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET positive at the end of treatment. Only one patient overall changed regimens following PET2.

Dr. Samaeekia’s team concluded that PET2 scan results “did not have any meaningful impact” on patient management or outcomes.

During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Dr. Hutchings, from the Rigshospitalet in Copenhagen, pointed out that 4 of the 12 PET2-positive patients treated at Loma Linda were still PET positive at the end of treatment.

Even so, Dr. Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make “us feel better,” but it ultimately doesn’t “make any difference in our management.”

In the AHOD1331 study, “the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative,” added session comoderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester (N.Y.) Medical Center.

The study by Dr. Samaeekia and colleagues was internally funded. Dr. Samaeekia reports no relevant financial relationships. Dr. Hutchings has previously reported consultancy and research funding from numerous companies. Dr. Friedberg reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

FROM SOHO 2023

It may be possible for patients with Hodgkin lymphoma to safely skip their interim PET-CT scan (PET2) following two cycles of frontline brentuximab vedotin (Adcetris), according to research presented at the annual meeting of the Society of Hematologic Oncology in Houston.

Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda (Calif.) University Medical Center.

These studies, including one conducted by Dr. Samaeekia’s team, provide “evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin,” Dr. Samaeekia, who presented the data, concluded.

Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.

However, “there are obviously challenges associated with implementing a PET-guided approach,” said Dr. Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients’ risk for toxicities when treatment is escalated based on the scan results.

Given these caveats, Dr. Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.

Dr. Samaeekia’s team analyzed findings from three trials – ECHELON-1, AHOD1331, and BREACH – which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.

In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2 negative (94.9% vs. 90.6%; hazard ratio for death, 0.54) as well as those who were PET2 positive (95% vs. 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.

In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab – 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab “eliminated the predictive value of the interim PET assessment.” The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.

Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Dr. Samaeekia and colleagues found that 24 were PET2 negative and 12 were PET2 positive. All patients who were PET2 negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET positive at the end of treatment. Only one patient overall changed regimens following PET2.

Dr. Samaeekia’s team concluded that PET2 scan results “did not have any meaningful impact” on patient management or outcomes.

During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Dr. Hutchings, from the Rigshospitalet in Copenhagen, pointed out that 4 of the 12 PET2-positive patients treated at Loma Linda were still PET positive at the end of treatment.

Even so, Dr. Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make “us feel better,” but it ultimately doesn’t “make any difference in our management.”

In the AHOD1331 study, “the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative,” added session comoderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester (N.Y.) Medical Center.

The study by Dr. Samaeekia and colleagues was internally funded. Dr. Samaeekia reports no relevant financial relationships. Dr. Hutchings has previously reported consultancy and research funding from numerous companies. Dr. Friedberg reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

FROM SOHO 2023

It may be possible for patients with Hodgkin lymphoma to safely skip their interim PET-CT scan (PET2) following two cycles of frontline brentuximab vedotin (Adcetris), according to research presented at the annual meeting of the Society of Hematologic Oncology in Houston.

Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda (Calif.) University Medical Center.

These studies, including one conducted by Dr. Samaeekia’s team, provide “evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin,” Dr. Samaeekia, who presented the data, concluded.

Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.

However, “there are obviously challenges associated with implementing a PET-guided approach,” said Dr. Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients’ risk for toxicities when treatment is escalated based on the scan results.

Given these caveats, Dr. Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.

Dr. Samaeekia’s team analyzed findings from three trials – ECHELON-1, AHOD1331, and BREACH – which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.

In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2 negative (94.9% vs. 90.6%; hazard ratio for death, 0.54) as well as those who were PET2 positive (95% vs. 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.

In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab – 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab “eliminated the predictive value of the interim PET assessment.” The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.

Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Dr. Samaeekia and colleagues found that 24 were PET2 negative and 12 were PET2 positive. All patients who were PET2 negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET positive at the end of treatment. Only one patient overall changed regimens following PET2.

Dr. Samaeekia’s team concluded that PET2 scan results “did not have any meaningful impact” on patient management or outcomes.

During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Dr. Hutchings, from the Rigshospitalet in Copenhagen, pointed out that 4 of the 12 PET2-positive patients treated at Loma Linda were still PET positive at the end of treatment.

Even so, Dr. Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make “us feel better,” but it ultimately doesn’t “make any difference in our management.”

In the AHOD1331 study, “the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative,” added session comoderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester (N.Y.) Medical Center.

The study by Dr. Samaeekia and colleagues was internally funded. Dr. Samaeekia reports no relevant financial relationships. Dr. Hutchings has previously reported consultancy and research funding from numerous companies. Dr. Friedberg reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with cutaneous Merkel cell carcinoma (MCC) have a higher risk of subsequently developing solid and hematologic cancers, according to a new analysis.

In a cohort of 6,146 patients with a first primary MCC, a total of 725 (11.8%) developed subsequent primary cancers. For solid tumors, the risk was highest for cutaneous melanoma and papillary thyroid carcinoma, while for hematologic cancers, the risk was increased for non-Hodgkin lymphoma.

“Our study does confirm that patients with MCC are at higher risk for developing other cancers,” study author Lisa C. Zaba, MD, PhD, associate professor of dermatology and director of the Merkel cell carcinoma multidisciplinary clinic, Stanford (Calif.) Cancer Center, said in an interview. “MCC is a highly malignant cancer with a 40% recurrence risk.”

Because of this high risk, Dr. Zaba noted that patients with MCC get frequent surveillance with both imaging studies (PET-CT and CT) as well as frequent visits in clinic with MCC experts. “Specifically, a patient with MCC is imaged and seen in clinic every 3-6 months for the first 3 years after diagnosis, and every 6-12 months thereafter for up to 5 years,” she said. “Interestingly, this high level of surveillance may be one reason that we find so many cancers in patients who have been diagnosed with MCC, compared to the general population.”

The study was published online in JAMA Dermatology.

With the death of “Margaritaville” singer Jimmy Buffett, who recently died of MCC 4 years after his diagnosis, this rare, aggressive skin cancer has been put in the spotlight. Survival has been increasing, primarily because of the advent of immunotherapy, and the authors note that it is therefore imperative to better understand the risk of subsequent primary tumors to inform screening and treatment recommendations.

In this cohort study, Dr. Zaba and colleagues identified 6,146 patients from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program who had been diagnosed with a first primary cutaneous MCC between 2000 and 2018.

Endpoints were the ratio of observed to expected number of cases of subsequent cancer (Standardized incidence ratio, or SIR) and the excess risk.

Overall, there was an elevated risk of developing a subsequent primary cancer after being diagnosed with MCC (SIR, 1.28; excess risk, 57.25 per 10,000 person-years). This included the risk for all solid tumors including liver (SIR, 1.92; excess risk, 2.77 per 10,000 person-years), pancreas (SIR, 1.65; excess risk, 4.55 per 10,000 person-years), cutaneous melanoma (SIR, 2.36; excess risk, 15.27 per 10,000 person-years), and kidney (SIR, 1.64; excess risk, 3.83 per 10,000 person-years).

There was also a higher risk of developing papillary thyroid carcinoma (PTC) (SIR, 5.26; excess risk, 6.16 per 10,000 person-years).

The risk of developing hematological cancers after MCC was also increased, especially for non-Hodgkin lymphoma (SIR, 2.62; excess risk, 15.48 per 10,000 person-years) and myelodysplastic syndrome (SIR, 2.17; excess risk, 2.73 per 10,000 person-years).

The risk for developing subsequent tumors, including melanoma and non-Hodgkin lymphoma, remained significant for up to 10 years, while the risk for developing PTC and kidney cancers remained for up to 5 years.

“After 3-5 years, when a MCC patient’s risk of MCC recurrence drops below 2%, we do not currently have guidelines in place for additional cancer screening,” Dr. Zaba said. “Regarding patient education, patients with MCC are educated to let us know if they experience any symptoms of cancer between visits, including unintentional weight loss, night sweats, headaches that increasingly worsen, or growing lumps or bumps. These symptoms may occur in a multitude of cancers and not just MCC.”

Weighing in on the study, Jeffrey M. Farma, MD, interim chair, department of surgical oncology at Fox Chase Cancer Center, Philadelphia, noted that MCC is considered to be high risk because of its chances of recurring after surgical resection or spreading to lymph nodes or other areas of the body. “There are approximately 3,000 new cases of melanoma a year in the U.S., and it is 40 times rarer than melanoma,” he said. “Patients are usually diagnosed with Merkel cell carcinoma later in life, and the tumors have been associated with sun exposure and immunosuppression and have also been associated with the polyomavirus.”

That said, however, he emphasized that great strides have been made in treatment. “These tumors are very sensitive to radiation, and we generally treat earlier-stage MCC with a combination of surgery and radiation therapy,” said Dr. Farma. “More recently we have had a lot of success with the use of immunotherapy to treat more advanced MCC.”

Dr. Zaba reported receiving grants from the Kuni Foundation outside the submitted work. No other disclosures were reported. Author Eleni Linos, MD, DrPH, MPH, is supported by grant K24AR075060 from the National Institutes of Health. No other outside funding was reported. Dr. Farma had no disclosures.

Patients with cutaneous Merkel cell carcinoma (MCC) have a higher risk of subsequently developing solid and hematologic cancers, according to a new analysis.

In a cohort of 6,146 patients with a first primary MCC, a total of 725 (11.8%) developed subsequent primary cancers. For solid tumors, the risk was highest for cutaneous melanoma and papillary thyroid carcinoma, while for hematologic cancers, the risk was increased for non-Hodgkin lymphoma.

“Our study does confirm that patients with MCC are at higher risk for developing other cancers,” study author Lisa C. Zaba, MD, PhD, associate professor of dermatology and director of the Merkel cell carcinoma multidisciplinary clinic, Stanford (Calif.) Cancer Center, said in an interview. “MCC is a highly malignant cancer with a 40% recurrence risk.”

Because of this high risk, Dr. Zaba noted that patients with MCC get frequent surveillance with both imaging studies (PET-CT and CT) as well as frequent visits in clinic with MCC experts. “Specifically, a patient with MCC is imaged and seen in clinic every 3-6 months for the first 3 years after diagnosis, and every 6-12 months thereafter for up to 5 years,” she said. “Interestingly, this high level of surveillance may be one reason that we find so many cancers in patients who have been diagnosed with MCC, compared to the general population.”

The study was published online in JAMA Dermatology.

With the death of “Margaritaville” singer Jimmy Buffett, who recently died of MCC 4 years after his diagnosis, this rare, aggressive skin cancer has been put in the spotlight. Survival has been increasing, primarily because of the advent of immunotherapy, and the authors note that it is therefore imperative to better understand the risk of subsequent primary tumors to inform screening and treatment recommendations.

In this cohort study, Dr. Zaba and colleagues identified 6,146 patients from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program who had been diagnosed with a first primary cutaneous MCC between 2000 and 2018.

Endpoints were the ratio of observed to expected number of cases of subsequent cancer (Standardized incidence ratio, or SIR) and the excess risk.

Overall, there was an elevated risk of developing a subsequent primary cancer after being diagnosed with MCC (SIR, 1.28; excess risk, 57.25 per 10,000 person-years). This included the risk for all solid tumors including liver (SIR, 1.92; excess risk, 2.77 per 10,000 person-years), pancreas (SIR, 1.65; excess risk, 4.55 per 10,000 person-years), cutaneous melanoma (SIR, 2.36; excess risk, 15.27 per 10,000 person-years), and kidney (SIR, 1.64; excess risk, 3.83 per 10,000 person-years).

There was also a higher risk of developing papillary thyroid carcinoma (PTC) (SIR, 5.26; excess risk, 6.16 per 10,000 person-years).

The risk of developing hematological cancers after MCC was also increased, especially for non-Hodgkin lymphoma (SIR, 2.62; excess risk, 15.48 per 10,000 person-years) and myelodysplastic syndrome (SIR, 2.17; excess risk, 2.73 per 10,000 person-years).

The risk for developing subsequent tumors, including melanoma and non-Hodgkin lymphoma, remained significant for up to 10 years, while the risk for developing PTC and kidney cancers remained for up to 5 years.

“After 3-5 years, when a MCC patient’s risk of MCC recurrence drops below 2%, we do not currently have guidelines in place for additional cancer screening,” Dr. Zaba said. “Regarding patient education, patients with MCC are educated to let us know if they experience any symptoms of cancer between visits, including unintentional weight loss, night sweats, headaches that increasingly worsen, or growing lumps or bumps. These symptoms may occur in a multitude of cancers and not just MCC.”

Weighing in on the study, Jeffrey M. Farma, MD, interim chair, department of surgical oncology at Fox Chase Cancer Center, Philadelphia, noted that MCC is considered to be high risk because of its chances of recurring after surgical resection or spreading to lymph nodes or other areas of the body. “There are approximately 3,000 new cases of melanoma a year in the U.S., and it is 40 times rarer than melanoma,” he said. “Patients are usually diagnosed with Merkel cell carcinoma later in life, and the tumors have been associated with sun exposure and immunosuppression and have also been associated with the polyomavirus.”

That said, however, he emphasized that great strides have been made in treatment. “These tumors are very sensitive to radiation, and we generally treat earlier-stage MCC with a combination of surgery and radiation therapy,” said Dr. Farma. “More recently we have had a lot of success with the use of immunotherapy to treat more advanced MCC.”

Dr. Zaba reported receiving grants from the Kuni Foundation outside the submitted work. No other disclosures were reported. Author Eleni Linos, MD, DrPH, MPH, is supported by grant K24AR075060 from the National Institutes of Health. No other outside funding was reported. Dr. Farma had no disclosures.

Patients with cutaneous Merkel cell carcinoma (MCC) have a higher risk of subsequently developing solid and hematologic cancers, according to a new analysis.

In a cohort of 6,146 patients with a first primary MCC, a total of 725 (11.8%) developed subsequent primary cancers. For solid tumors, the risk was highest for cutaneous melanoma and papillary thyroid carcinoma, while for hematologic cancers, the risk was increased for non-Hodgkin lymphoma.

“Our study does confirm that patients with MCC are at higher risk for developing other cancers,” study author Lisa C. Zaba, MD, PhD, associate professor of dermatology and director of the Merkel cell carcinoma multidisciplinary clinic, Stanford (Calif.) Cancer Center, said in an interview. “MCC is a highly malignant cancer with a 40% recurrence risk.”

Because of this high risk, Dr. Zaba noted that patients with MCC get frequent surveillance with both imaging studies (PET-CT and CT) as well as frequent visits in clinic with MCC experts. “Specifically, a patient with MCC is imaged and seen in clinic every 3-6 months for the first 3 years after diagnosis, and every 6-12 months thereafter for up to 5 years,” she said. “Interestingly, this high level of surveillance may be one reason that we find so many cancers in patients who have been diagnosed with MCC, compared to the general population.”

The study was published online in JAMA Dermatology.

With the death of “Margaritaville” singer Jimmy Buffett, who recently died of MCC 4 years after his diagnosis, this rare, aggressive skin cancer has been put in the spotlight. Survival has been increasing, primarily because of the advent of immunotherapy, and the authors note that it is therefore imperative to better understand the risk of subsequent primary tumors to inform screening and treatment recommendations.

In this cohort study, Dr. Zaba and colleagues identified 6,146 patients from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program who had been diagnosed with a first primary cutaneous MCC between 2000 and 2018.

Endpoints were the ratio of observed to expected number of cases of subsequent cancer (Standardized incidence ratio, or SIR) and the excess risk.

Overall, there was an elevated risk of developing a subsequent primary cancer after being diagnosed with MCC (SIR, 1.28; excess risk, 57.25 per 10,000 person-years). This included the risk for all solid tumors including liver (SIR, 1.92; excess risk, 2.77 per 10,000 person-years), pancreas (SIR, 1.65; excess risk, 4.55 per 10,000 person-years), cutaneous melanoma (SIR, 2.36; excess risk, 15.27 per 10,000 person-years), and kidney (SIR, 1.64; excess risk, 3.83 per 10,000 person-years).

There was also a higher risk of developing papillary thyroid carcinoma (PTC) (SIR, 5.26; excess risk, 6.16 per 10,000 person-years).

The risk of developing hematological cancers after MCC was also increased, especially for non-Hodgkin lymphoma (SIR, 2.62; excess risk, 15.48 per 10,000 person-years) and myelodysplastic syndrome (SIR, 2.17; excess risk, 2.73 per 10,000 person-years).

The risk for developing subsequent tumors, including melanoma and non-Hodgkin lymphoma, remained significant for up to 10 years, while the risk for developing PTC and kidney cancers remained for up to 5 years.

“After 3-5 years, when a MCC patient’s risk of MCC recurrence drops below 2%, we do not currently have guidelines in place for additional cancer screening,” Dr. Zaba said. “Regarding patient education, patients with MCC are educated to let us know if they experience any symptoms of cancer between visits, including unintentional weight loss, night sweats, headaches that increasingly worsen, or growing lumps or bumps. These symptoms may occur in a multitude of cancers and not just MCC.”

Weighing in on the study, Jeffrey M. Farma, MD, interim chair, department of surgical oncology at Fox Chase Cancer Center, Philadelphia, noted that MCC is considered to be high risk because of its chances of recurring after surgical resection or spreading to lymph nodes or other areas of the body. “There are approximately 3,000 new cases of melanoma a year in the U.S., and it is 40 times rarer than melanoma,” he said. “Patients are usually diagnosed with Merkel cell carcinoma later in life, and the tumors have been associated with sun exposure and immunosuppression and have also been associated with the polyomavirus.”

That said, however, he emphasized that great strides have been made in treatment. “These tumors are very sensitive to radiation, and we generally treat earlier-stage MCC with a combination of surgery and radiation therapy,” said Dr. Farma. “More recently we have had a lot of success with the use of immunotherapy to treat more advanced MCC.”

Dr. Zaba reported receiving grants from the Kuni Foundation outside the submitted work. No other disclosures were reported. Author Eleni Linos, MD, DrPH, MPH, is supported by grant K24AR075060 from the National Institutes of Health. No other outside funding was reported. Dr. Farma had no disclosures.

SINGAPORE – Can the prolonged use of skin-lightening products, such as hydroquinone, lead to skin cancer?

This question was posed by Ousmane Faye, MD, PhD, director general of Mali’s Bamako Dermatology Hospital, at the World Congress of Dermatology. 

Dr. Faye explored the issue during a hot topics session at the meeting, prefacing that it was an important question to ask because “in West Africa, skin bleaching is very common.”

“There are many local names” for skin bleaching, he said. “For example, in Senegal, it’s called xessal; in Mali and Ivory Coast, its name is caco; in South Africa, there are many names, like ukutsheyisa.”

Skin bleaching refers to the cosmetic misuse of topical agents to change one’s natural skin color. It’s a centuries-old practice that people, mainly women, adopt “to increase attractiveness and self-esteem,” explained Dr. Faye.

To demonstrate how pervasive skin bleaching is on the continent, he presented a slide that summarized figures from six studies spanning the past 2 decades. Prevalence ranged from 25% in Mali (based on a 1993 survey of 210 women) to a high of 79.25% in Benin (from a sample size of 511 women in 2019). In other studies of women in Burkina Faso and Togo, the figures were 44.3% and 58.9%, respectively. The most recently conducted study, which involved 2,689 Senegalese women and was published in 2022, found that nearly 6 in 10 (59.2%) respondents used skin-lightening products.

But skin bleaching isn’t just limited to Africa, said session moderator Omar Lupi, MD, PhD, associate professor of dermatology at the Federal University of the State of Rio de Janeiro, when approached for an independent comment. “It’s a traditional practice around the world. Maybe not in the developed countries, but it’s quite common in Africa, in South America, and in Asia.”

His sentiments are echoed in a meta-analysis that was published in the International Journal of Dermatology in 2019. The work examined 68 studies involving more than 67,000 people across Africa, Asia, Europe, the Middle East, and North America. It found that the pooled lifetime prevalence of skin bleaching was 27.7% (95% confidence interval, 19.6-37.5; P < .01).

“This is an important and interesting topic because our world is shrinking,” Dr. Lupi told this news organization. “Even in countries that don’t have bleaching as a common situation, we now have patients who are migrating from one part [of the world] to another, so bleaching is something that can knock on your door and you need to be prepared.”

Misuse leads to complications

The issue is pertinent to dermatologists because skin bleaching is associated with a wide range of complications. Take, for example, topical steroids, which are the most common products used for bleaching, said Dr. Faye in his talk. 

“Clobetasol can suppress the hypothalamic-pituitary-adrenal (HPA) function,” he said, referring to the body’s main stress response system. “It can also foster skin infection, including bacterial, fungal, viral, and parasitic infection.”

In addition, topical steroids that are misused as skin lighteners have been reported to cause stretch marks, skin atrophy, inflammatory acne, and even metabolic disorders such as diabetes and hypertension, said Dr. Faye.

To further his point, he cited a 2021 prospective case-control study conducted across five sub-Saharan countries, which found that the use of “voluntary cosmetic depigmentation” significantly increased a person’s risk for necrotizing fasciitis of the lower limbs (odds ratio, 2.29; 95% CI, 1.19-3.73; P = .0226).

Similarly, mercury, another substance found in products commonly used to bleach skin, has been associated with problems ranging from rashes to renal toxicity. And because it’s so incredibly harmful, mercury is also known to cause neurologic abnormalities. 

Apart from causing certain conditions, prolonged use of skin-lightening products can change the way existing diseases present themselves as well as their severity, added Dr. Faye. 
 

An increased risk

But what about skin bleaching’s link with cancer? “Skin cancer on Black skin is uncommon, yet it occurs in skin-bleaching women,” said Dr. Faye.

“Since 2000, we have had some cases of skin cancer associated with skin bleaching,” he continued, adding that squamous cell carcinoma (SCC) is the most frequent type of cancer observed. 

If you look at what’s been published on the topic so far, you’ll see that “all the cases of skin cancer are located over the neck or some exposed area when skin bleaching products are used for more than 10 years,” said Dr. Faye. “And most of the time, the age of the patient ranges from 30 to 60 years.”

The first known case in Africa was reported in a 58-year-old woman from Ghana, who had been using skin bleaching products for close to 30 years. The patient presented with tumors on her face, neck, and arms.

Dr. Faye then proceeded to share more than 10 such carcinoma cases. “These previous reports strongly suggest a relationship between skin bleaching and skin cancers,” said Dr. Faye.

Indeed, there have been reports and publications in the literature that support his observation, including one last year, which found that use of the tyrosinase inhibitor hydroquinone was associated with approximately a threefold increased risk for skin cancer.

For some, including Brazil’s Dr. Lupi, Dr. Faye’s talk was enlightening: “I didn’t know about this relationship [of bleaching] with skin cancer, it was something new for me.”

But the prevalence of SCC is very low, compared with that of skin bleaching, Dr. Faye acknowledged. Moreover, the cancer observed in the cases reported could have resulted from a number of reasons, including exposure to harmful ultraviolet rays from the sun and genetic predisposition in addition to the use of bleaching products such as hydroquinone. “Other causes of skin cancer are not excluded,” he said.

To further explore the link between skin bleaching and cancer, “we need case-control studies to provide more evidence,” he added. Until then, dermatologists “should keep on promoting messages” to prevent SCC from occurring. This includes encouraging the use of proper sun protection in addition to discouraging the practice of skin bleaching, which still persists despite more than 10 African nations banning the use of toxic skin-lightening products.

Dr. Faye and Dr. Lupi report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SINGAPORE – Can the prolonged use of skin-lightening products, such as hydroquinone, lead to skin cancer?

This question was posed by Ousmane Faye, MD, PhD, director general of Mali’s Bamako Dermatology Hospital, at the World Congress of Dermatology. 

Dr. Faye explored the issue during a hot topics session at the meeting, prefacing that it was an important question to ask because “in West Africa, skin bleaching is very common.”

“There are many local names” for skin bleaching, he said. “For example, in Senegal, it’s called xessal; in Mali and Ivory Coast, its name is caco; in South Africa, there are many names, like ukutsheyisa.”

Skin bleaching refers to the cosmetic misuse of topical agents to change one’s natural skin color. It’s a centuries-old practice that people, mainly women, adopt “to increase attractiveness and self-esteem,” explained Dr. Faye.

To demonstrate how pervasive skin bleaching is on the continent, he presented a slide that summarized figures from six studies spanning the past 2 decades. Prevalence ranged from 25% in Mali (based on a 1993 survey of 210 women) to a high of 79.25% in Benin (from a sample size of 511 women in 2019). In other studies of women in Burkina Faso and Togo, the figures were 44.3% and 58.9%, respectively. The most recently conducted study, which involved 2,689 Senegalese women and was published in 2022, found that nearly 6 in 10 (59.2%) respondents used skin-lightening products.

But skin bleaching isn’t just limited to Africa, said session moderator Omar Lupi, MD, PhD, associate professor of dermatology at the Federal University of the State of Rio de Janeiro, when approached for an independent comment. “It’s a traditional practice around the world. Maybe not in the developed countries, but it’s quite common in Africa, in South America, and in Asia.”

His sentiments are echoed in a meta-analysis that was published in the International Journal of Dermatology in 2019. The work examined 68 studies involving more than 67,000 people across Africa, Asia, Europe, the Middle East, and North America. It found that the pooled lifetime prevalence of skin bleaching was 27.7% (95% confidence interval, 19.6-37.5; P < .01).

“This is an important and interesting topic because our world is shrinking,” Dr. Lupi told this news organization. “Even in countries that don’t have bleaching as a common situation, we now have patients who are migrating from one part [of the world] to another, so bleaching is something that can knock on your door and you need to be prepared.”

Misuse leads to complications

The issue is pertinent to dermatologists because skin bleaching is associated with a wide range of complications. Take, for example, topical steroids, which are the most common products used for bleaching, said Dr. Faye in his talk. 

“Clobetasol can suppress the hypothalamic-pituitary-adrenal (HPA) function,” he said, referring to the body’s main stress response system. “It can also foster skin infection, including bacterial, fungal, viral, and parasitic infection.”

In addition, topical steroids that are misused as skin lighteners have been reported to cause stretch marks, skin atrophy, inflammatory acne, and even metabolic disorders such as diabetes and hypertension, said Dr. Faye.

To further his point, he cited a 2021 prospective case-control study conducted across five sub-Saharan countries, which found that the use of “voluntary cosmetic depigmentation” significantly increased a person’s risk for necrotizing fasciitis of the lower limbs (odds ratio, 2.29; 95% CI, 1.19-3.73; P = .0226).

Similarly, mercury, another substance found in products commonly used to bleach skin, has been associated with problems ranging from rashes to renal toxicity. And because it’s so incredibly harmful, mercury is also known to cause neurologic abnormalities. 

Apart from causing certain conditions, prolonged use of skin-lightening products can change the way existing diseases present themselves as well as their severity, added Dr. Faye. 
 

An increased risk

But what about skin bleaching’s link with cancer? “Skin cancer on Black skin is uncommon, yet it occurs in skin-bleaching women,” said Dr. Faye.

“Since 2000, we have had some cases of skin cancer associated with skin bleaching,” he continued, adding that squamous cell carcinoma (SCC) is the most frequent type of cancer observed. 

If you look at what’s been published on the topic so far, you’ll see that “all the cases of skin cancer are located over the neck or some exposed area when skin bleaching products are used for more than 10 years,” said Dr. Faye. “And most of the time, the age of the patient ranges from 30 to 60 years.”

The first known case in Africa was reported in a 58-year-old woman from Ghana, who had been using skin bleaching products for close to 30 years. The patient presented with tumors on her face, neck, and arms.

Dr. Faye then proceeded to share more than 10 such carcinoma cases. “These previous reports strongly suggest a relationship between skin bleaching and skin cancers,” said Dr. Faye.

Indeed, there have been reports and publications in the literature that support his observation, including one last year, which found that use of the tyrosinase inhibitor hydroquinone was associated with approximately a threefold increased risk for skin cancer.

For some, including Brazil’s Dr. Lupi, Dr. Faye’s talk was enlightening: “I didn’t know about this relationship [of bleaching] with skin cancer, it was something new for me.”

But the prevalence of SCC is very low, compared with that of skin bleaching, Dr. Faye acknowledged. Moreover, the cancer observed in the cases reported could have resulted from a number of reasons, including exposure to harmful ultraviolet rays from the sun and genetic predisposition in addition to the use of bleaching products such as hydroquinone. “Other causes of skin cancer are not excluded,” he said.

To further explore the link between skin bleaching and cancer, “we need case-control studies to provide more evidence,” he added. Until then, dermatologists “should keep on promoting messages” to prevent SCC from occurring. This includes encouraging the use of proper sun protection in addition to discouraging the practice of skin bleaching, which still persists despite more than 10 African nations banning the use of toxic skin-lightening products.

Dr. Faye and Dr. Lupi report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SINGAPORE – Can the prolonged use of skin-lightening products, such as hydroquinone, lead to skin cancer?

This question was posed by Ousmane Faye, MD, PhD, director general of Mali’s Bamako Dermatology Hospital, at the World Congress of Dermatology. 

Dr. Faye explored the issue during a hot topics session at the meeting, prefacing that it was an important question to ask because “in West Africa, skin bleaching is very common.”

“There are many local names” for skin bleaching, he said. “For example, in Senegal, it’s called xessal; in Mali and Ivory Coast, its name is caco; in South Africa, there are many names, like ukutsheyisa.”

Skin bleaching refers to the cosmetic misuse of topical agents to change one’s natural skin color. It’s a centuries-old practice that people, mainly women, adopt “to increase attractiveness and self-esteem,” explained Dr. Faye.

To demonstrate how pervasive skin bleaching is on the continent, he presented a slide that summarized figures from six studies spanning the past 2 decades. Prevalence ranged from 25% in Mali (based on a 1993 survey of 210 women) to a high of 79.25% in Benin (from a sample size of 511 women in 2019). In other studies of women in Burkina Faso and Togo, the figures were 44.3% and 58.9%, respectively. The most recently conducted study, which involved 2,689 Senegalese women and was published in 2022, found that nearly 6 in 10 (59.2%) respondents used skin-lightening products.

But skin bleaching isn’t just limited to Africa, said session moderator Omar Lupi, MD, PhD, associate professor of dermatology at the Federal University of the State of Rio de Janeiro, when approached for an independent comment. “It’s a traditional practice around the world. Maybe not in the developed countries, but it’s quite common in Africa, in South America, and in Asia.”

His sentiments are echoed in a meta-analysis that was published in the International Journal of Dermatology in 2019. The work examined 68 studies involving more than 67,000 people across Africa, Asia, Europe, the Middle East, and North America. It found that the pooled lifetime prevalence of skin bleaching was 27.7% (95% confidence interval, 19.6-37.5; P < .01).

“This is an important and interesting topic because our world is shrinking,” Dr. Lupi told this news organization. “Even in countries that don’t have bleaching as a common situation, we now have patients who are migrating from one part [of the world] to another, so bleaching is something that can knock on your door and you need to be prepared.”

Misuse leads to complications

The issue is pertinent to dermatologists because skin bleaching is associated with a wide range of complications. Take, for example, topical steroids, which are the most common products used for bleaching, said Dr. Faye in his talk. 

“Clobetasol can suppress the hypothalamic-pituitary-adrenal (HPA) function,” he said, referring to the body’s main stress response system. “It can also foster skin infection, including bacterial, fungal, viral, and parasitic infection.”

In addition, topical steroids that are misused as skin lighteners have been reported to cause stretch marks, skin atrophy, inflammatory acne, and even metabolic disorders such as diabetes and hypertension, said Dr. Faye.

To further his point, he cited a 2021 prospective case-control study conducted across five sub-Saharan countries, which found that the use of “voluntary cosmetic depigmentation” significantly increased a person’s risk for necrotizing fasciitis of the lower limbs (odds ratio, 2.29; 95% CI, 1.19-3.73; P = .0226).

Similarly, mercury, another substance found in products commonly used to bleach skin, has been associated with problems ranging from rashes to renal toxicity. And because it’s so incredibly harmful, mercury is also known to cause neurologic abnormalities. 

Apart from causing certain conditions, prolonged use of skin-lightening products can change the way existing diseases present themselves as well as their severity, added Dr. Faye. 
 

An increased risk

But what about skin bleaching’s link with cancer? “Skin cancer on Black skin is uncommon, yet it occurs in skin-bleaching women,” said Dr. Faye.

“Since 2000, we have had some cases of skin cancer associated with skin bleaching,” he continued, adding that squamous cell carcinoma (SCC) is the most frequent type of cancer observed. 

If you look at what’s been published on the topic so far, you’ll see that “all the cases of skin cancer are located over the neck or some exposed area when skin bleaching products are used for more than 10 years,” said Dr. Faye. “And most of the time, the age of the patient ranges from 30 to 60 years.”

The first known case in Africa was reported in a 58-year-old woman from Ghana, who had been using skin bleaching products for close to 30 years. The patient presented with tumors on her face, neck, and arms.

Dr. Faye then proceeded to share more than 10 such carcinoma cases. “These previous reports strongly suggest a relationship between skin bleaching and skin cancers,” said Dr. Faye.

Indeed, there have been reports and publications in the literature that support his observation, including one last year, which found that use of the tyrosinase inhibitor hydroquinone was associated with approximately a threefold increased risk for skin cancer.

For some, including Brazil’s Dr. Lupi, Dr. Faye’s talk was enlightening: “I didn’t know about this relationship [of bleaching] with skin cancer, it was something new for me.”

But the prevalence of SCC is very low, compared with that of skin bleaching, Dr. Faye acknowledged. Moreover, the cancer observed in the cases reported could have resulted from a number of reasons, including exposure to harmful ultraviolet rays from the sun and genetic predisposition in addition to the use of bleaching products such as hydroquinone. “Other causes of skin cancer are not excluded,” he said.

To further explore the link between skin bleaching and cancer, “we need case-control studies to provide more evidence,” he added. Until then, dermatologists “should keep on promoting messages” to prevent SCC from occurring. This includes encouraging the use of proper sun protection in addition to discouraging the practice of skin bleaching, which still persists despite more than 10 African nations banning the use of toxic skin-lightening products.

Dr. Faye and Dr. Lupi report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pleural mesothelioma is generally treated by extended pleurectomy decortication, and there has been little improvement in systemic treatment of early-stage, resectable mesothelioma, which has led to the recommendations of maximum cytoreduction. U.S. and European guidelines, as well as an international consensus statement, support this approach, but it has never been tested in a randomized, controlled trial.

Now it has, and the result is surprising: Surgery led to reduced survival and more serious adverse events, compared with chemotherapy alone. The conclusion was uncomfortable for Eric Lim, MD, who presented the results of the MARS2 trial at the annual World Conference on Lung Cancer. “Ladies and gentlemen, as a surgeon standing here, you have no idea how much it pains me to conclude that extended pleurectomy decortication, an operation that we have been offering for over 70 years, has been associated with a higher risk of death, more serious complications, poorer quality of life, and higher costs, compared to mesothelioma patients who were randomized to chemotherapy alone,” said Dr. Lim of the Royal Brompton Hospital, London, during his presentation.

Although the line drew laughter and applause from the audience, Paula Ugalde Figueroa, MD, who served as a discussant, raised some concerns about the study. Disease presence in one hemithorax was assessed only by chest CT scan, which is notorious for underestimating the volume of disease during surgery. There was also no information on pleural effusion or how many patients received it prior to intervention. Existing guidelines suggest staging of mesothelioma should also use PET scans, and invasive mediastinal staging should be assessed with endobronchial ultrasound. “None of these were performed during the trial,” said Dr. Figueroa, who is an associate thoracic surgeon at Brigham and Women’s Hospital, Boston. “At this point, my question is, are the arms of this study well balanced in regard to tumor volume? We don’t know,” she added.

Dr. Figueroa noted that the 90-day mortality seemed higher than that seen in other studies. “So, does the surgeon’s experience and center volume affect the outcome of this study?” she asked. Dr. Figueroa personally made phone calls to the participating centers and found that 45% of the patients in the trial were treated at low-volume centers, defined by her as two to three patients per year. “Should we assume that their surgical outcomes are similar between those centers? In this trial, with approximately half of patients from low-volume centers, extended pleurectomy decortication for mesothelioma had no significant difference when compared to those patients that underwent chemotherapy alone. Would the outcome be different in exclusively high-volume centers?” she concluded.

The study randomized 335 patients to receive surgery and chemotherapy, or chemotherapy alone. They received two cycles of platinum-based chemotherapy and pemetrexed prior to surgery and up to four cycles after surgery. The average age was 69 years; 86.9% were male, and 85.7% of tumors were epithelioid only. Among those in the surgery group, 88.5% underwent extended pleurectomy/decortication, 8.3% underwent pleurectomy decortication, 1.9% underwent partial pleurectomy, 0.6% exploration with no pleurodesis, and 0.6% were classified as “other” surgery. Completeness of resection was R0 in 3.2% of surgeries, R1 in 80.9%, and R2 in 15.9%. In-hospital mortality occurred in 3.8% of patients, and postsurgical 90-day mortality was 8.9%.

Over the first 42 months of follow-up, the hazard ratio for overall survival was 1.28 in the no-surgery group (P = .03). “The survival was so good in this early-stage cohort that we had to extend the trial by 6 months to get the prerequisite number of deaths, underscoring the phenomenal importance of having a randomized comparative cohort for all future studies on surgery for mesothelioma,” said Dr. Lim.

After 42 months, there was no survival difference between the two groups (hazard ratio, 0.48; P = .15). Dr. Lim attributed the change at 42 months to the fact that only 15 patients remained in each arm at that stage. There was no significant difference between the two groups with respect to progression-free survival.

The survival benefit of the no-surgery group was sustained after additional analyses, including adjustment of the number of first-line chemotherapy cycles and immunotherapy received after completion of the trial protocol.

Adverse events were more common in the surgery group (incidence rate ratio, 3.6; P < .001), including any cardiac disorder (IRR, 2.73; 95% confidence interval, 1.11-6.67); any infection or infestation (IRR, 1.99; 95% CI, 1.33-2.99); any respiratory, thoracic, or mediastinal disorder (IRR, 2.40; 95% CI, 1.52-3.80); and any surgical or medical procedure (IRR, 2.23; 95% CI, 1.04-4.78). The EORTC quality of life score favored the nonsurgery group at 6 weeks, but there was no significant difference at other time points.

Dr. Lim and Dr. Figueroa have no relevant financial disclosures.

Pleural mesothelioma is generally treated by extended pleurectomy decortication, and there has been little improvement in systemic treatment of early-stage, resectable mesothelioma, which has led to the recommendations of maximum cytoreduction. U.S. and European guidelines, as well as an international consensus statement, support this approach, but it has never been tested in a randomized, controlled trial.

Now it has, and the result is surprising: Surgery led to reduced survival and more serious adverse events, compared with chemotherapy alone. The conclusion was uncomfortable for Eric Lim, MD, who presented the results of the MARS2 trial at the annual World Conference on Lung Cancer. “Ladies and gentlemen, as a surgeon standing here, you have no idea how much it pains me to conclude that extended pleurectomy decortication, an operation that we have been offering for over 70 years, has been associated with a higher risk of death, more serious complications, poorer quality of life, and higher costs, compared to mesothelioma patients who were randomized to chemotherapy alone,” said Dr. Lim of the Royal Brompton Hospital, London, during his presentation.

Although the line drew laughter and applause from the audience, Paula Ugalde Figueroa, MD, who served as a discussant, raised some concerns about the study. Disease presence in one hemithorax was assessed only by chest CT scan, which is notorious for underestimating the volume of disease during surgery. There was also no information on pleural effusion or how many patients received it prior to intervention. Existing guidelines suggest staging of mesothelioma should also use PET scans, and invasive mediastinal staging should be assessed with endobronchial ultrasound. “None of these were performed during the trial,” said Dr. Figueroa, who is an associate thoracic surgeon at Brigham and Women’s Hospital, Boston. “At this point, my question is, are the arms of this study well balanced in regard to tumor volume? We don’t know,” she added.

Dr. Figueroa noted that the 90-day mortality seemed higher than that seen in other studies. “So, does the surgeon’s experience and center volume affect the outcome of this study?” she asked. Dr. Figueroa personally made phone calls to the participating centers and found that 45% of the patients in the trial were treated at low-volume centers, defined by her as two to three patients per year. “Should we assume that their surgical outcomes are similar between those centers? In this trial, with approximately half of patients from low-volume centers, extended pleurectomy decortication for mesothelioma had no significant difference when compared to those patients that underwent chemotherapy alone. Would the outcome be different in exclusively high-volume centers?” she concluded.

The study randomized 335 patients to receive surgery and chemotherapy, or chemotherapy alone. They received two cycles of platinum-based chemotherapy and pemetrexed prior to surgery and up to four cycles after surgery. The average age was 69 years; 86.9% were male, and 85.7% of tumors were epithelioid only. Among those in the surgery group, 88.5% underwent extended pleurectomy/decortication, 8.3% underwent pleurectomy decortication, 1.9% underwent partial pleurectomy, 0.6% exploration with no pleurodesis, and 0.6% were classified as “other” surgery. Completeness of resection was R0 in 3.2% of surgeries, R1 in 80.9%, and R2 in 15.9%. In-hospital mortality occurred in 3.8% of patients, and postsurgical 90-day mortality was 8.9%.

Over the first 42 months of follow-up, the hazard ratio for overall survival was 1.28 in the no-surgery group (P = .03). “The survival was so good in this early-stage cohort that we had to extend the trial by 6 months to get the prerequisite number of deaths, underscoring the phenomenal importance of having a randomized comparative cohort for all future studies on surgery for mesothelioma,” said Dr. Lim.

After 42 months, there was no survival difference between the two groups (hazard ratio, 0.48; P = .15). Dr. Lim attributed the change at 42 months to the fact that only 15 patients remained in each arm at that stage. There was no significant difference between the two groups with respect to progression-free survival.

The survival benefit of the no-surgery group was sustained after additional analyses, including adjustment of the number of first-line chemotherapy cycles and immunotherapy received after completion of the trial protocol.

Adverse events were more common in the surgery group (incidence rate ratio, 3.6; P < .001), including any cardiac disorder (IRR, 2.73; 95% confidence interval, 1.11-6.67); any infection or infestation (IRR, 1.99; 95% CI, 1.33-2.99); any respiratory, thoracic, or mediastinal disorder (IRR, 2.40; 95% CI, 1.52-3.80); and any surgical or medical procedure (IRR, 2.23; 95% CI, 1.04-4.78). The EORTC quality of life score favored the nonsurgery group at 6 weeks, but there was no significant difference at other time points.

Dr. Lim and Dr. Figueroa have no relevant financial disclosures.

Pleural mesothelioma is generally treated by extended pleurectomy decortication, and there has been little improvement in systemic treatment of early-stage, resectable mesothelioma, which has led to the recommendations of maximum cytoreduction. U.S. and European guidelines, as well as an international consensus statement, support this approach, but it has never been tested in a randomized, controlled trial.

Now it has, and the result is surprising: Surgery led to reduced survival and more serious adverse events, compared with chemotherapy alone. The conclusion was uncomfortable for Eric Lim, MD, who presented the results of the MARS2 trial at the annual World Conference on Lung Cancer. “Ladies and gentlemen, as a surgeon standing here, you have no idea how much it pains me to conclude that extended pleurectomy decortication, an operation that we have been offering for over 70 years, has been associated with a higher risk of death, more serious complications, poorer quality of life, and higher costs, compared to mesothelioma patients who were randomized to chemotherapy alone,” said Dr. Lim of the Royal Brompton Hospital, London, during his presentation.

Although the line drew laughter and applause from the audience, Paula Ugalde Figueroa, MD, who served as a discussant, raised some concerns about the study. Disease presence in one hemithorax was assessed only by chest CT scan, which is notorious for underestimating the volume of disease during surgery. There was also no information on pleural effusion or how many patients received it prior to intervention. Existing guidelines suggest staging of mesothelioma should also use PET scans, and invasive mediastinal staging should be assessed with endobronchial ultrasound. “None of these were performed during the trial,” said Dr. Figueroa, who is an associate thoracic surgeon at Brigham and Women’s Hospital, Boston. “At this point, my question is, are the arms of this study well balanced in regard to tumor volume? We don’t know,” she added.

Dr. Figueroa noted that the 90-day mortality seemed higher than that seen in other studies. “So, does the surgeon’s experience and center volume affect the outcome of this study?” she asked. Dr. Figueroa personally made phone calls to the participating centers and found that 45% of the patients in the trial were treated at low-volume centers, defined by her as two to three patients per year. “Should we assume that their surgical outcomes are similar between those centers? In this trial, with approximately half of patients from low-volume centers, extended pleurectomy decortication for mesothelioma had no significant difference when compared to those patients that underwent chemotherapy alone. Would the outcome be different in exclusively high-volume centers?” she concluded.

The study randomized 335 patients to receive surgery and chemotherapy, or chemotherapy alone. They received two cycles of platinum-based chemotherapy and pemetrexed prior to surgery and up to four cycles after surgery. The average age was 69 years; 86.9% were male, and 85.7% of tumors were epithelioid only. Among those in the surgery group, 88.5% underwent extended pleurectomy/decortication, 8.3% underwent pleurectomy decortication, 1.9% underwent partial pleurectomy, 0.6% exploration with no pleurodesis, and 0.6% were classified as “other” surgery. Completeness of resection was R0 in 3.2% of surgeries, R1 in 80.9%, and R2 in 15.9%. In-hospital mortality occurred in 3.8% of patients, and postsurgical 90-day mortality was 8.9%.

Over the first 42 months of follow-up, the hazard ratio for overall survival was 1.28 in the no-surgery group (P = .03). “The survival was so good in this early-stage cohort that we had to extend the trial by 6 months to get the prerequisite number of deaths, underscoring the phenomenal importance of having a randomized comparative cohort for all future studies on surgery for mesothelioma,” said Dr. Lim.

After 42 months, there was no survival difference between the two groups (hazard ratio, 0.48; P = .15). Dr. Lim attributed the change at 42 months to the fact that only 15 patients remained in each arm at that stage. There was no significant difference between the two groups with respect to progression-free survival.

The survival benefit of the no-surgery group was sustained after additional analyses, including adjustment of the number of first-line chemotherapy cycles and immunotherapy received after completion of the trial protocol.

Adverse events were more common in the surgery group (incidence rate ratio, 3.6; P < .001), including any cardiac disorder (IRR, 2.73; 95% confidence interval, 1.11-6.67); any infection or infestation (IRR, 1.99; 95% CI, 1.33-2.99); any respiratory, thoracic, or mediastinal disorder (IRR, 2.40; 95% CI, 1.52-3.80); and any surgical or medical procedure (IRR, 2.23; 95% CI, 1.04-4.78). The EORTC quality of life score favored the nonsurgery group at 6 weeks, but there was no significant difference at other time points.

Dr. Lim and Dr. Figueroa have no relevant financial disclosures.

What happens to grief when those around you don’t understand it? Where does it go? How do you process it?

Disenfranchised grief, when someone or society more generally doesn’t see a loss as worthy of mourning, can deprive people of experiencing or processing their sadness. This grief, which may be triggered by the death of an ex-spouse, a pet, a failed adoption, can be painful and long-lasting.

Here, we reflect as physicians on our own experiences and memories of this phenomenon.
 

Suzanne Cole, MD: ‘I didn’t feel the right to grieve’

During the COVID-19 pandemic, my little sister unexpectedly died. Though she was not one of the nearly 7 million people who died of the virus, in 2021 she became another type of statistic: one of the 109,699 people in the United State who died from a drug overdose. Hers was from fentanyl laced with methamphetamines.

Her death unraveled me. I felt deep guilt that I could not pull her from the sweeping current that had wrenched her from mainstream society into the underbelly of sex work and toward the solace of mind-altering drugs.

But I did not feel the right to grieve for her as I have grieved for other loved ones who were not blamed for their exit from this world. My sister was living a sordid life on the fringes of society. My grief felt invalid, undeserved. Yet, in the eyes of other “upstanding citizens,” her life was not as worth grieving – or so I thought. I tucked my sorrow into a small corner of my soul so no one would see, and I carried on.

To this day, the shame I feel robbed me of the ability to freely talk about her or share the searing pain I feel. Tears still prick my eyes when I think of her, but I have become adept at swallowing them, shaking off the waves of grief as though nothing happened. Even now, I cannot shake the pervasive feeling that my silent tears don’t deserve to be wept.
 

Don S. Dizon, MD: Working through tragedy

As a medical student, I worked with an outpatient physician as part of a third-year rotation. When we met, the first thing that struck me was how disheveled he looked. His clothes were wrinkled, and his pants were baggy. He took cigarette breaks, which I found disturbing.

But I quickly came to admire him. Despite my first impression, he was the type of doctor I aspired to be. He didn’t need to look at a patient’s chart to recall who they were. He just knew them. He greeted patients warmly, asked about their family. He even remembered the special occasions his patients had mentioned since their past visit. He epitomized empathy and connectedness.

Spending one day in clinic brought to light the challenges of forming such bonds with patients. A man came into the cancer clinic reporting chest pain and was triaged to an exam room. Soon after, the patient was found unresponsive on the floor. Nurses were yelling for help, and the doctor ran in and started CPR while minutes ticked by waiting for an ambulance that could take him to the ED.

By the time help arrived, the patient was blue.

He had died in the clinic in the middle of the day, as the waiting room filled. After the body was taken away, the doctor went into the bathroom. About 20 minutes later, he came out, eyes bloodshot, and continued with the rest of his day, ensuring each patient was seen and cared for.

As a medical student, it hit me how hard it must be to see something so tragic like the end of a life and then continue with your day as if nothing had happened. This is an experience of grief I later came to know well after nearly 30 years treating patients with advanced cancers: compartmentalizing it and carrying on.
 

A space for grieving: The Schwartz Center Rounds

Disenfranchised grief, the grief that is hard to share and often seems wrong to feel in the first place, can be triggered in many situations. Losing a person others don’t believe deserve to be grieved, such as an abusive partner or someone who committed a crime; losing someone you cared for in a professional role; a loss experienced in a breakup or same-sex partnership, if that relationship was not accepted by one’s family; loss from infertility, miscarriage, stillbirth, or failed adoption; loss that may be taboo or stigmatized, such as deaths via suicide or abortion; and loss of a job, home, or possession that you treasure.

Many of us have had similar situations or will, and the feeling that no one understands the need to mourn can be paralyzing and alienating. In the early days, intense, crushing feelings can cause intrusive, distracting thoughts, and over time, that grief can linger and find a permanent place in our minds.

More and more, though, we are being given opportunities to reflect on these sad moments.

The Schwartz Rounds are an example of such an opportunity. In these rounds, we gather to talk about the experience of caring for people, not the science of medicine.

During one particularly powerful rounds, I spoke to my colleagues about my initial meeting with a patient who was very sick. I detailed the experience of telling her children and her at that initial consult how I thought she was dying and that I did not recommend therapy. I remember how they cried. And I remembered how powerless I felt.

As I recalled that memory during Schwartz Rounds, I could not stop from crying. The unfairness of being a physician meeting someone for the first time and having to tell them such bad news overwhelmed me.

Even more poignant, I had the chance to reconnect with this woman’s children, who were present that day, not as audience members but as participants. Their presence may have brought my emotions to the surface more strongly. In that moment, I could show them the feelings I had bottled up for the sake of professionalism. Ultimately, I felt relieved, freer somehow, as if this burden my soul was carrying had been lifted.

Although we are both grateful for forums like this, these opportunities to share and express the grief we may have hidden away are not as common as they should be.

As physicians, we may express grief by shedding tears at the bedside of a patient nearing the end of life or through the anxiety we feel when our patient suffers a severe reaction to treatment. But we tend to put it away, to go on with our day, because there are others to be seen and cared for and more work to be done. Somehow, we move forward, shedding tears in one room and celebrating victories in another.

We need to create more spaces to express and feel grief, so we don’t get lost in it. Because understanding how grief impacts us, as people and as providers, is one of the most important realizations we can make as we go about our time-honored profession as healers.

Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute, director of medical oncology at Rhode Island Hospital, and a professor of medicine at Brown University, all in Providence. He reported conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol-Myers Squibb, and Kazia.

A version of this article first appeared on Medscape.com.

What happens to grief when those around you don’t understand it? Where does it go? How do you process it?

Disenfranchised grief, when someone or society more generally doesn’t see a loss as worthy of mourning, can deprive people of experiencing or processing their sadness. This grief, which may be triggered by the death of an ex-spouse, a pet, a failed adoption, can be painful and long-lasting.

Here, we reflect as physicians on our own experiences and memories of this phenomenon.
 

Suzanne Cole, MD: ‘I didn’t feel the right to grieve’

During the COVID-19 pandemic, my little sister unexpectedly died. Though she was not one of the nearly 7 million people who died of the virus, in 2021 she became another type of statistic: one of the 109,699 people in the United State who died from a drug overdose. Hers was from fentanyl laced with methamphetamines.

Her death unraveled me. I felt deep guilt that I could not pull her from the sweeping current that had wrenched her from mainstream society into the underbelly of sex work and toward the solace of mind-altering drugs.

But I did not feel the right to grieve for her as I have grieved for other loved ones who were not blamed for their exit from this world. My sister was living a sordid life on the fringes of society. My grief felt invalid, undeserved. Yet, in the eyes of other “upstanding citizens,” her life was not as worth grieving – or so I thought. I tucked my sorrow into a small corner of my soul so no one would see, and I carried on.

To this day, the shame I feel robbed me of the ability to freely talk about her or share the searing pain I feel. Tears still prick my eyes when I think of her, but I have become adept at swallowing them, shaking off the waves of grief as though nothing happened. Even now, I cannot shake the pervasive feeling that my silent tears don’t deserve to be wept.
 

Don S. Dizon, MD: Working through tragedy

As a medical student, I worked with an outpatient physician as part of a third-year rotation. When we met, the first thing that struck me was how disheveled he looked. His clothes were wrinkled, and his pants were baggy. He took cigarette breaks, which I found disturbing.

But I quickly came to admire him. Despite my first impression, he was the type of doctor I aspired to be. He didn’t need to look at a patient’s chart to recall who they were. He just knew them. He greeted patients warmly, asked about their family. He even remembered the special occasions his patients had mentioned since their past visit. He epitomized empathy and connectedness.

Spending one day in clinic brought to light the challenges of forming such bonds with patients. A man came into the cancer clinic reporting chest pain and was triaged to an exam room. Soon after, the patient was found unresponsive on the floor. Nurses were yelling for help, and the doctor ran in and started CPR while minutes ticked by waiting for an ambulance that could take him to the ED.

By the time help arrived, the patient was blue.

He had died in the clinic in the middle of the day, as the waiting room filled. After the body was taken away, the doctor went into the bathroom. About 20 minutes later, he came out, eyes bloodshot, and continued with the rest of his day, ensuring each patient was seen and cared for.

As a medical student, it hit me how hard it must be to see something so tragic like the end of a life and then continue with your day as if nothing had happened. This is an experience of grief I later came to know well after nearly 30 years treating patients with advanced cancers: compartmentalizing it and carrying on.
 

A space for grieving: The Schwartz Center Rounds

Disenfranchised grief, the grief that is hard to share and often seems wrong to feel in the first place, can be triggered in many situations. Losing a person others don’t believe deserve to be grieved, such as an abusive partner or someone who committed a crime; losing someone you cared for in a professional role; a loss experienced in a breakup or same-sex partnership, if that relationship was not accepted by one’s family; loss from infertility, miscarriage, stillbirth, or failed adoption; loss that may be taboo or stigmatized, such as deaths via suicide or abortion; and loss of a job, home, or possession that you treasure.

Many of us have had similar situations or will, and the feeling that no one understands the need to mourn can be paralyzing and alienating. In the early days, intense, crushing feelings can cause intrusive, distracting thoughts, and over time, that grief can linger and find a permanent place in our minds.

More and more, though, we are being given opportunities to reflect on these sad moments.

The Schwartz Rounds are an example of such an opportunity. In these rounds, we gather to talk about the experience of caring for people, not the science of medicine.

During one particularly powerful rounds, I spoke to my colleagues about my initial meeting with a patient who was very sick. I detailed the experience of telling her children and her at that initial consult how I thought she was dying and that I did not recommend therapy. I remember how they cried. And I remembered how powerless I felt.

As I recalled that memory during Schwartz Rounds, I could not stop from crying. The unfairness of being a physician meeting someone for the first time and having to tell them such bad news overwhelmed me.

Even more poignant, I had the chance to reconnect with this woman’s children, who were present that day, not as audience members but as participants. Their presence may have brought my emotions to the surface more strongly. In that moment, I could show them the feelings I had bottled up for the sake of professionalism. Ultimately, I felt relieved, freer somehow, as if this burden my soul was carrying had been lifted.

Although we are both grateful for forums like this, these opportunities to share and express the grief we may have hidden away are not as common as they should be.

As physicians, we may express grief by shedding tears at the bedside of a patient nearing the end of life or through the anxiety we feel when our patient suffers a severe reaction to treatment. But we tend to put it away, to go on with our day, because there are others to be seen and cared for and more work to be done. Somehow, we move forward, shedding tears in one room and celebrating victories in another.

We need to create more spaces to express and feel grief, so we don’t get lost in it. Because understanding how grief impacts us, as people and as providers, is one of the most important realizations we can make as we go about our time-honored profession as healers.

Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute, director of medical oncology at Rhode Island Hospital, and a professor of medicine at Brown University, all in Providence. He reported conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol-Myers Squibb, and Kazia.

A version of this article first appeared on Medscape.com.

What happens to grief when those around you don’t understand it? Where does it go? How do you process it?

Disenfranchised grief, when someone or society more generally doesn’t see a loss as worthy of mourning, can deprive people of experiencing or processing their sadness. This grief, which may be triggered by the death of an ex-spouse, a pet, a failed adoption, can be painful and long-lasting.

Here, we reflect as physicians on our own experiences and memories of this phenomenon.
 

Suzanne Cole, MD: ‘I didn’t feel the right to grieve’

During the COVID-19 pandemic, my little sister unexpectedly died. Though she was not one of the nearly 7 million people who died of the virus, in 2021 she became another type of statistic: one of the 109,699 people in the United State who died from a drug overdose. Hers was from fentanyl laced with methamphetamines.

Her death unraveled me. I felt deep guilt that I could not pull her from the sweeping current that had wrenched her from mainstream society into the underbelly of sex work and toward the solace of mind-altering drugs.

But I did not feel the right to grieve for her as I have grieved for other loved ones who were not blamed for their exit from this world. My sister was living a sordid life on the fringes of society. My grief felt invalid, undeserved. Yet, in the eyes of other “upstanding citizens,” her life was not as worth grieving – or so I thought. I tucked my sorrow into a small corner of my soul so no one would see, and I carried on.

To this day, the shame I feel robbed me of the ability to freely talk about her or share the searing pain I feel. Tears still prick my eyes when I think of her, but I have become adept at swallowing them, shaking off the waves of grief as though nothing happened. Even now, I cannot shake the pervasive feeling that my silent tears don’t deserve to be wept.
 

Don S. Dizon, MD: Working through tragedy

As a medical student, I worked with an outpatient physician as part of a third-year rotation. When we met, the first thing that struck me was how disheveled he looked. His clothes were wrinkled, and his pants were baggy. He took cigarette breaks, which I found disturbing.

But I quickly came to admire him. Despite my first impression, he was the type of doctor I aspired to be. He didn’t need to look at a patient’s chart to recall who they were. He just knew them. He greeted patients warmly, asked about their family. He even remembered the special occasions his patients had mentioned since their past visit. He epitomized empathy and connectedness.

Spending one day in clinic brought to light the challenges of forming such bonds with patients. A man came into the cancer clinic reporting chest pain and was triaged to an exam room. Soon after, the patient was found unresponsive on the floor. Nurses were yelling for help, and the doctor ran in and started CPR while minutes ticked by waiting for an ambulance that could take him to the ED.

By the time help arrived, the patient was blue.

He had died in the clinic in the middle of the day, as the waiting room filled. After the body was taken away, the doctor went into the bathroom. About 20 minutes later, he came out, eyes bloodshot, and continued with the rest of his day, ensuring each patient was seen and cared for.

As a medical student, it hit me how hard it must be to see something so tragic like the end of a life and then continue with your day as if nothing had happened. This is an experience of grief I later came to know well after nearly 30 years treating patients with advanced cancers: compartmentalizing it and carrying on.
 

A space for grieving: The Schwartz Center Rounds

Disenfranchised grief, the grief that is hard to share and often seems wrong to feel in the first place, can be triggered in many situations. Losing a person others don’t believe deserve to be grieved, such as an abusive partner or someone who committed a crime; losing someone you cared for in a professional role; a loss experienced in a breakup or same-sex partnership, if that relationship was not accepted by one’s family; loss from infertility, miscarriage, stillbirth, or failed adoption; loss that may be taboo or stigmatized, such as deaths via suicide or abortion; and loss of a job, home, or possession that you treasure.

Many of us have had similar situations or will, and the feeling that no one understands the need to mourn can be paralyzing and alienating. In the early days, intense, crushing feelings can cause intrusive, distracting thoughts, and over time, that grief can linger and find a permanent place in our minds.

More and more, though, we are being given opportunities to reflect on these sad moments.

The Schwartz Rounds are an example of such an opportunity. In these rounds, we gather to talk about the experience of caring for people, not the science of medicine.

During one particularly powerful rounds, I spoke to my colleagues about my initial meeting with a patient who was very sick. I detailed the experience of telling her children and her at that initial consult how I thought she was dying and that I did not recommend therapy. I remember how they cried. And I remembered how powerless I felt.

As I recalled that memory during Schwartz Rounds, I could not stop from crying. The unfairness of being a physician meeting someone for the first time and having to tell them such bad news overwhelmed me.

Even more poignant, I had the chance to reconnect with this woman’s children, who were present that day, not as audience members but as participants. Their presence may have brought my emotions to the surface more strongly. In that moment, I could show them the feelings I had bottled up for the sake of professionalism. Ultimately, I felt relieved, freer somehow, as if this burden my soul was carrying had been lifted.

Although we are both grateful for forums like this, these opportunities to share and express the grief we may have hidden away are not as common as they should be.

As physicians, we may express grief by shedding tears at the bedside of a patient nearing the end of life or through the anxiety we feel when our patient suffers a severe reaction to treatment. But we tend to put it away, to go on with our day, because there are others to be seen and cared for and more work to be done. Somehow, we move forward, shedding tears in one room and celebrating victories in another.

We need to create more spaces to express and feel grief, so we don’t get lost in it. Because understanding how grief impacts us, as people and as providers, is one of the most important realizations we can make as we go about our time-honored profession as healers.

Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute, director of medical oncology at Rhode Island Hospital, and a professor of medicine at Brown University, all in Providence. He reported conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol-Myers Squibb, and Kazia.

A version of this article first appeared on Medscape.com.

Antibody-drug conjugates (ADC) link a tumor-targeted antibody to a cytotoxic drug through a chemical linker and hold the promise of high potency. This has led to a burgeoning interest in solid tumors, with over 100 clinical trials in progress. Non–small cell lung cancer (NSCLC) is no exception. In 2022, the Food and Drug Administration approved trastuzumab DXd for pretreated NSCLC patients with HER2-mutant tumors. Two others have lung cancer breakthrough therapy designations from the FDA, including patritumab deruxtecan (HER3-DXd) for EGFR-mutant NSCLC and telisotuzumab vedotin for NSCLC that overexpresses c-Met.

At the annual World Conference on Lung Cancer, researchers outlined some of the latest developments in ADCs targeting the antigens HER3, trophoblast cell-surface antigen 2 (TROP-2), and the B7-H3 immunoregulatory protein, as single agents or in combination with immunotherapy. Following the presentations, discussant Helena Linardou, MD, PhD, emphasized the need for pharmacogenomics to predict toxicity and studies to understand resistance mechanisms. “ADCs are a new, rapidly evolving class of therapeutics, and I think that we will all have to be prepared for the future that is coming,” said Dr. Linardou, who is director of the 4th oncology department and the Comprehensive Clinical Trials Center at Metropolitan Hospital in Athens.

Researchers presented four ADC clinical trial updates.
 

Patritumab deruxtecan

Patritumab deruxtecan (Daiichi Sankyo) links a HER3 antibody to the topoisomerase I inhibitor deruxtecan (HER3-DXd). In the open-label, phase 2 HERTHENA-Lung01 trial, it was tested in patients with NSCLC EGFR-activation mutations, which occurs in 14%-38% of NSCLC cases. There are few options for these patients following failure of EGFR tyrosine kinase inhibitor therapy.

The study included 225 patients previously treated with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy who received 5.6 mg/kg of HER3-DXd every 3 weeks. Over a median follow-up of 13.1 months and a median treatment duration of 5.5 months), 29.8% had a confirmed overall response (95% confidence interval, 23.9%-36.2%) with a median duration of 6.4 months (95% CI, 4.9-7.8). The median progression-free survival was 5.5 months (95% CI, 5.1-5.9), and the median OS was 11.9 months (95% CI, 11.2-13.1). The researchers noted similar outcomes among patients with different mechanisms of EGFR TKI resistance. The frequency of adverse events was similar to previous studies, with drug-related adverse events linked to treatment discontinuation of 7.1% interstitial lung disease in 5.3%. Among 30 patients with brain metastases, the confirmed intracranial response rate was 33.3% (95% CI, 17.3%-52.8%).

The study was published simultaneously online in the Journal of Clinical Oncology. (Abstract)
 

Datopotamab deruxtecan

PD-1/PD-L1 inhibitors are the first-line therapy for metastatic NSCLC, but there are efforts to improve outcomes through combination therapy. Datopotamab deruxtecan (Dato-DXd, Daiichi Sankyo, AstraZeneca) is an ADC targeting TROP2, and it has been shown in preclinical studies to enhance tumor responses to PD-1/PD-L1 inhibitors. The ADC improved progression-free survival (PFS), compared with docetaxel, in previously treated advanced or metastatic NSCLC.

In an interim analysis of the phase 1b TROPION-Lung04 study, researchers reported results from the combination of Dato-DXd with durvalumab with or without carboplatin. The study included 38 patients, some of whom had previously undergone treatment with immune checkpoint inhibitors. Nineteen patients received the doublet, and 14 received the carboplatin triplet. Grade 3 or higher treatment-emergent adverse events occurred in 42.1% of the doublet group and 71.4% of the triplet group. Interstitial lung disease occurred in 15.8% and 7.1% of the two groups, respectively. The objective response rate was 50.0% in the doublet group and 76.9% in the triplet group. The disease control rate was 92.9% and 92.3%, respectively. Durable responses occurred in both the first-line setting and the overall population. (Abstract)
 

Sacituzumab govitecan

Another ADC being tested with PD-1/PD-L1 inhibitors is sacituzumab govitecan (Trodelvy, Gilead), which has already received FDA approval for metastatic triple-negative breast cancer, pretreated HR+/HER2- metastatic breast cancer, and metastatic urothelial cancer. Like datopotamab, sacituzumab targets TROP-2. Researchers reported preliminary results from the phase 2 EVOKE-02 study, in which the ADC was combined with pembrolizumab for the first-line treatment of metastatic NSCLC. The overall response rate was 56% (95% CI, 42%-69%). Among patients with PD-L1 tumor proportion score (TPS) ≥ 50%, the ORR was 69% (95% CI, 49%-85%) and 44% (95% CI, 26%-62%) among those with TPS < 50%. The disease control rate was 86% (95% CI, 68%-96%) and 78% (95% CI, 60%-91%), respectively. The most frequent treatment-emergent adverse events (TEAEs) were diarrhea, anemia, and asthenia, and 18% of patients discontinued the study drug because of TEAEs. (Abstract)

Ifinatamab deruxtecan

Ifinatamab deruxtecan (Daiichi Sankyo) targets the B7-H3 antigen, which is an immunoregulatory protein that is overexpressed in many tumors. In the DS7300-A-J101 study, it was tested in patients with advanced or metastatic solid tumors, without selection for B7-H3 expression. A subgroup analysis of 22 patients with small cell lung cancer (SCLC) showed an ORR of 52.4 (95% CI, 29.8-74.3), a complete response of 4.8%, and a partial response in 47.6%. The median PFS was 5.6 months (95% CI, 3.9-8.1) and median OS was 12.2 months (95% CI, 6.4-not applicable). The most common treatment-emergent adverse events were nausea (59.1%), fatigue (50.0%), anemia (27.3%), vomiting (27.3%), and decreased appetite (22.7%). (Abstract)

Antibody-drug conjugates (ADC) link a tumor-targeted antibody to a cytotoxic drug through a chemical linker and hold the promise of high potency. This has led to a burgeoning interest in solid tumors, with over 100 clinical trials in progress. Non–small cell lung cancer (NSCLC) is no exception. In 2022, the Food and Drug Administration approved trastuzumab DXd for pretreated NSCLC patients with HER2-mutant tumors. Two others have lung cancer breakthrough therapy designations from the FDA, including patritumab deruxtecan (HER3-DXd) for EGFR-mutant NSCLC and telisotuzumab vedotin for NSCLC that overexpresses c-Met.

At the annual World Conference on Lung Cancer, researchers outlined some of the latest developments in ADCs targeting the antigens HER3, trophoblast cell-surface antigen 2 (TROP-2), and the B7-H3 immunoregulatory protein, as single agents or in combination with immunotherapy. Following the presentations, discussant Helena Linardou, MD, PhD, emphasized the need for pharmacogenomics to predict toxicity and studies to understand resistance mechanisms. “ADCs are a new, rapidly evolving class of therapeutics, and I think that we will all have to be prepared for the future that is coming,” said Dr. Linardou, who is director of the 4th oncology department and the Comprehensive Clinical Trials Center at Metropolitan Hospital in Athens.

Researchers presented four ADC clinical trial updates.
 

Patritumab deruxtecan

Patritumab deruxtecan (Daiichi Sankyo) links a HER3 antibody to the topoisomerase I inhibitor deruxtecan (HER3-DXd). In the open-label, phase 2 HERTHENA-Lung01 trial, it was tested in patients with NSCLC EGFR-activation mutations, which occurs in 14%-38% of NSCLC cases. There are few options for these patients following failure of EGFR tyrosine kinase inhibitor therapy.

The study included 225 patients previously treated with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy who received 5.6 mg/kg of HER3-DXd every 3 weeks. Over a median follow-up of 13.1 months and a median treatment duration of 5.5 months), 29.8% had a confirmed overall response (95% confidence interval, 23.9%-36.2%) with a median duration of 6.4 months (95% CI, 4.9-7.8). The median progression-free survival was 5.5 months (95% CI, 5.1-5.9), and the median OS was 11.9 months (95% CI, 11.2-13.1). The researchers noted similar outcomes among patients with different mechanisms of EGFR TKI resistance. The frequency of adverse events was similar to previous studies, with drug-related adverse events linked to treatment discontinuation of 7.1% interstitial lung disease in 5.3%. Among 30 patients with brain metastases, the confirmed intracranial response rate was 33.3% (95% CI, 17.3%-52.8%).

The study was published simultaneously online in the Journal of Clinical Oncology. (Abstract)
 

Datopotamab deruxtecan

PD-1/PD-L1 inhibitors are the first-line therapy for metastatic NSCLC, but there are efforts to improve outcomes through combination therapy. Datopotamab deruxtecan (Dato-DXd, Daiichi Sankyo, AstraZeneca) is an ADC targeting TROP2, and it has been shown in preclinical studies to enhance tumor responses to PD-1/PD-L1 inhibitors. The ADC improved progression-free survival (PFS), compared with docetaxel, in previously treated advanced or metastatic NSCLC.

In an interim analysis of the phase 1b TROPION-Lung04 study, researchers reported results from the combination of Dato-DXd with durvalumab with or without carboplatin. The study included 38 patients, some of whom had previously undergone treatment with immune checkpoint inhibitors. Nineteen patients received the doublet, and 14 received the carboplatin triplet. Grade 3 or higher treatment-emergent adverse events occurred in 42.1% of the doublet group and 71.4% of the triplet group. Interstitial lung disease occurred in 15.8% and 7.1% of the two groups, respectively. The objective response rate was 50.0% in the doublet group and 76.9% in the triplet group. The disease control rate was 92.9% and 92.3%, respectively. Durable responses occurred in both the first-line setting and the overall population. (Abstract)
 

Sacituzumab govitecan

Another ADC being tested with PD-1/PD-L1 inhibitors is sacituzumab govitecan (Trodelvy, Gilead), which has already received FDA approval for metastatic triple-negative breast cancer, pretreated HR+/HER2- metastatic breast cancer, and metastatic urothelial cancer. Like datopotamab, sacituzumab targets TROP-2. Researchers reported preliminary results from the phase 2 EVOKE-02 study, in which the ADC was combined with pembrolizumab for the first-line treatment of metastatic NSCLC. The overall response rate was 56% (95% CI, 42%-69%). Among patients with PD-L1 tumor proportion score (TPS) ≥ 50%, the ORR was 69% (95% CI, 49%-85%) and 44% (95% CI, 26%-62%) among those with TPS < 50%. The disease control rate was 86% (95% CI, 68%-96%) and 78% (95% CI, 60%-91%), respectively. The most frequent treatment-emergent adverse events (TEAEs) were diarrhea, anemia, and asthenia, and 18% of patients discontinued the study drug because of TEAEs. (Abstract)

Ifinatamab deruxtecan

Ifinatamab deruxtecan (Daiichi Sankyo) targets the B7-H3 antigen, which is an immunoregulatory protein that is overexpressed in many tumors. In the DS7300-A-J101 study, it was tested in patients with advanced or metastatic solid tumors, without selection for B7-H3 expression. A subgroup analysis of 22 patients with small cell lung cancer (SCLC) showed an ORR of 52.4 (95% CI, 29.8-74.3), a complete response of 4.8%, and a partial response in 47.6%. The median PFS was 5.6 months (95% CI, 3.9-8.1) and median OS was 12.2 months (95% CI, 6.4-not applicable). The most common treatment-emergent adverse events were nausea (59.1%), fatigue (50.0%), anemia (27.3%), vomiting (27.3%), and decreased appetite (22.7%). (Abstract)

Antibody-drug conjugates (ADC) link a tumor-targeted antibody to a cytotoxic drug through a chemical linker and hold the promise of high potency. This has led to a burgeoning interest in solid tumors, with over 100 clinical trials in progress. Non–small cell lung cancer (NSCLC) is no exception. In 2022, the Food and Drug Administration approved trastuzumab DXd for pretreated NSCLC patients with HER2-mutant tumors. Two others have lung cancer breakthrough therapy designations from the FDA, including patritumab deruxtecan (HER3-DXd) for EGFR-mutant NSCLC and telisotuzumab vedotin for NSCLC that overexpresses c-Met.

At the annual World Conference on Lung Cancer, researchers outlined some of the latest developments in ADCs targeting the antigens HER3, trophoblast cell-surface antigen 2 (TROP-2), and the B7-H3 immunoregulatory protein, as single agents or in combination with immunotherapy. Following the presentations, discussant Helena Linardou, MD, PhD, emphasized the need for pharmacogenomics to predict toxicity and studies to understand resistance mechanisms. “ADCs are a new, rapidly evolving class of therapeutics, and I think that we will all have to be prepared for the future that is coming,” said Dr. Linardou, who is director of the 4th oncology department and the Comprehensive Clinical Trials Center at Metropolitan Hospital in Athens.

Researchers presented four ADC clinical trial updates.
 

Patritumab deruxtecan

Patritumab deruxtecan (Daiichi Sankyo) links a HER3 antibody to the topoisomerase I inhibitor deruxtecan (HER3-DXd). In the open-label, phase 2 HERTHENA-Lung01 trial, it was tested in patients with NSCLC EGFR-activation mutations, which occurs in 14%-38% of NSCLC cases. There are few options for these patients following failure of EGFR tyrosine kinase inhibitor therapy.

The study included 225 patients previously treated with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy who received 5.6 mg/kg of HER3-DXd every 3 weeks. Over a median follow-up of 13.1 months and a median treatment duration of 5.5 months), 29.8% had a confirmed overall response (95% confidence interval, 23.9%-36.2%) with a median duration of 6.4 months (95% CI, 4.9-7.8). The median progression-free survival was 5.5 months (95% CI, 5.1-5.9), and the median OS was 11.9 months (95% CI, 11.2-13.1). The researchers noted similar outcomes among patients with different mechanisms of EGFR TKI resistance. The frequency of adverse events was similar to previous studies, with drug-related adverse events linked to treatment discontinuation of 7.1% interstitial lung disease in 5.3%. Among 30 patients with brain metastases, the confirmed intracranial response rate was 33.3% (95% CI, 17.3%-52.8%).

The study was published simultaneously online in the Journal of Clinical Oncology. (Abstract)
 

Datopotamab deruxtecan

PD-1/PD-L1 inhibitors are the first-line therapy for metastatic NSCLC, but there are efforts to improve outcomes through combination therapy. Datopotamab deruxtecan (Dato-DXd, Daiichi Sankyo, AstraZeneca) is an ADC targeting TROP2, and it has been shown in preclinical studies to enhance tumor responses to PD-1/PD-L1 inhibitors. The ADC improved progression-free survival (PFS), compared with docetaxel, in previously treated advanced or metastatic NSCLC.

In an interim analysis of the phase 1b TROPION-Lung04 study, researchers reported results from the combination of Dato-DXd with durvalumab with or without carboplatin. The study included 38 patients, some of whom had previously undergone treatment with immune checkpoint inhibitors. Nineteen patients received the doublet, and 14 received the carboplatin triplet. Grade 3 or higher treatment-emergent adverse events occurred in 42.1% of the doublet group and 71.4% of the triplet group. Interstitial lung disease occurred in 15.8% and 7.1% of the two groups, respectively. The objective response rate was 50.0% in the doublet group and 76.9% in the triplet group. The disease control rate was 92.9% and 92.3%, respectively. Durable responses occurred in both the first-line setting and the overall population. (Abstract)
 

Sacituzumab govitecan

Another ADC being tested with PD-1/PD-L1 inhibitors is sacituzumab govitecan (Trodelvy, Gilead), which has already received FDA approval for metastatic triple-negative breast cancer, pretreated HR+/HER2- metastatic breast cancer, and metastatic urothelial cancer. Like datopotamab, sacituzumab targets TROP-2. Researchers reported preliminary results from the phase 2 EVOKE-02 study, in which the ADC was combined with pembrolizumab for the first-line treatment of metastatic NSCLC. The overall response rate was 56% (95% CI, 42%-69%). Among patients with PD-L1 tumor proportion score (TPS) ≥ 50%, the ORR was 69% (95% CI, 49%-85%) and 44% (95% CI, 26%-62%) among those with TPS < 50%. The disease control rate was 86% (95% CI, 68%-96%) and 78% (95% CI, 60%-91%), respectively. The most frequent treatment-emergent adverse events (TEAEs) were diarrhea, anemia, and asthenia, and 18% of patients discontinued the study drug because of TEAEs. (Abstract)

Ifinatamab deruxtecan

Ifinatamab deruxtecan (Daiichi Sankyo) targets the B7-H3 antigen, which is an immunoregulatory protein that is overexpressed in many tumors. In the DS7300-A-J101 study, it was tested in patients with advanced or metastatic solid tumors, without selection for B7-H3 expression. A subgroup analysis of 22 patients with small cell lung cancer (SCLC) showed an ORR of 52.4 (95% CI, 29.8-74.3), a complete response of 4.8%, and a partial response in 47.6%. The median PFS was 5.6 months (95% CI, 3.9-8.1) and median OS was 12.2 months (95% CI, 6.4-not applicable). The most common treatment-emergent adverse events were nausea (59.1%), fatigue (50.0%), anemia (27.3%), vomiting (27.3%), and decreased appetite (22.7%). (Abstract)

TOPLINE:

Implementing a post-surgery protocol that has undergone incremental changes over time significantly reduced inpatient and discharge opioid volumes while maintaining pain control after pancreatic cancer surgery.
 

METHODOLOGY:

• To reduce opioid dependence, misuse, and diversion, Centers for Disease Control and Prevention guidelines emphasize strategies to minimize opioid prescribing for managing pain. Still, opioid prescribing following surgery remains common practice.
• In the current study, a team of researchers implemented a recovery care pathway to reduce opioid use among 832 patients undergoing pancreatic resection at a comprehensive cancer center.
• The study evaluated three sequential protocols implemented over a period of about 6 years, from 2016 to 2022.
• In the final version, a standardized three-drug nonopioid bundle (acetaminophen, celecoxib, and methocarbamol) was initiated intravenously in the recovery room, after which the patient was given oral agents on postoperative day 1.
• The primary outcome measure was inpatient and discharge opioid volume in oral morphine equivalents (OMEs) across the three pathways.

TAKEAWAY:

• Opioid use significantly decreased with each sequential pathway refinement.
• For inpatients, total OME decreased by more than 55% across the pathways from a median of 290 mg to 184 mg and finally to 129 mg (P < .001).
• Median discharge OME dropped from 150 mg to 25 mg and then to 0 mg across the pathways (P < .001).
• With the final version of the pathway, more than half of patients (52.5%) had opioid-free discharges, compared with only 7.2% in the first pathway. Pain scores remained stable at 3 or less; the number of postdischarge refill requests was unchanged.

IN PRACTICE:

“Our findings suggest that reduction of postoperative opioid dissemination through opioid-free discharge after pancreatectomy and other major cancer operations may be realistic and feasible by following this no-cost blueprint,” the authors concluded. In an accompanying editorial, Melissa Hogg, MD, from NorthShore University Health System in Evanston, Ill., said the “study inspired me to update our institution’s [early recovery after surgery] protocol to reduce and eliminate opioid prescriptions.”
 

SOURCE:

The study was led by Ching-Wei D. Tzeng, MD, of the University of Texas MD Anderson Cancer Center, Houston. It was published online in JAMA Surgery.
 

LIMITATIONS:

The study evaluated the opioid protocol at a single center, which may limit the generalizability of the findings. The researchers did not receive patient feedback on pain control expectations or postoperative quality of life.
 

DISCLOSURES:

Dr. Tzeng reported receiving consultant fees and a sponsored research agreement from PanTher outside the submitted work. Dr. Hogg reported receiving training and travel funds from Intuitive Money. No other disclosures or outside funding were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Implementing a post-surgery protocol that has undergone incremental changes over time significantly reduced inpatient and discharge opioid volumes while maintaining pain control after pancreatic cancer surgery.
 

METHODOLOGY:

• To reduce opioid dependence, misuse, and diversion, Centers for Disease Control and Prevention guidelines emphasize strategies to minimize opioid prescribing for managing pain. Still, opioid prescribing following surgery remains common practice.
• In the current study, a team of researchers implemented a recovery care pathway to reduce opioid use among 832 patients undergoing pancreatic resection at a comprehensive cancer center.
• The study evaluated three sequential protocols implemented over a period of about 6 years, from 2016 to 2022.
• In the final version, a standardized three-drug nonopioid bundle (acetaminophen, celecoxib, and methocarbamol) was initiated intravenously in the recovery room, after which the patient was given oral agents on postoperative day 1.
• The primary outcome measure was inpatient and discharge opioid volume in oral morphine equivalents (OMEs) across the three pathways.

TAKEAWAY:

• Opioid use significantly decreased with each sequential pathway refinement.
• For inpatients, total OME decreased by more than 55% across the pathways from a median of 290 mg to 184 mg and finally to 129 mg (P < .001).
• Median discharge OME dropped from 150 mg to 25 mg and then to 0 mg across the pathways (P < .001).
• With the final version of the pathway, more than half of patients (52.5%) had opioid-free discharges, compared with only 7.2% in the first pathway. Pain scores remained stable at 3 or less; the number of postdischarge refill requests was unchanged.

IN PRACTICE:

“Our findings suggest that reduction of postoperative opioid dissemination through opioid-free discharge after pancreatectomy and other major cancer operations may be realistic and feasible by following this no-cost blueprint,” the authors concluded. In an accompanying editorial, Melissa Hogg, MD, from NorthShore University Health System in Evanston, Ill., said the “study inspired me to update our institution’s [early recovery after surgery] protocol to reduce and eliminate opioid prescriptions.”
 

SOURCE:

The study was led by Ching-Wei D. Tzeng, MD, of the University of Texas MD Anderson Cancer Center, Houston. It was published online in JAMA Surgery.
 

LIMITATIONS:

The study evaluated the opioid protocol at a single center, which may limit the generalizability of the findings. The researchers did not receive patient feedback on pain control expectations or postoperative quality of life.
 

DISCLOSURES:

Dr. Tzeng reported receiving consultant fees and a sponsored research agreement from PanTher outside the submitted work. Dr. Hogg reported receiving training and travel funds from Intuitive Money. No other disclosures or outside funding were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Implementing a post-surgery protocol that has undergone incremental changes over time significantly reduced inpatient and discharge opioid volumes while maintaining pain control after pancreatic cancer surgery.
 

METHODOLOGY:

• To reduce opioid dependence, misuse, and diversion, Centers for Disease Control and Prevention guidelines emphasize strategies to minimize opioid prescribing for managing pain. Still, opioid prescribing following surgery remains common practice.
• In the current study, a team of researchers implemented a recovery care pathway to reduce opioid use among 832 patients undergoing pancreatic resection at a comprehensive cancer center.
• The study evaluated three sequential protocols implemented over a period of about 6 years, from 2016 to 2022.
• In the final version, a standardized three-drug nonopioid bundle (acetaminophen, celecoxib, and methocarbamol) was initiated intravenously in the recovery room, after which the patient was given oral agents on postoperative day 1.
• The primary outcome measure was inpatient and discharge opioid volume in oral morphine equivalents (OMEs) across the three pathways.

TAKEAWAY:

• Opioid use significantly decreased with each sequential pathway refinement.
• For inpatients, total OME decreased by more than 55% across the pathways from a median of 290 mg to 184 mg and finally to 129 mg (P < .001).
• Median discharge OME dropped from 150 mg to 25 mg and then to 0 mg across the pathways (P < .001).
• With the final version of the pathway, more than half of patients (52.5%) had opioid-free discharges, compared with only 7.2% in the first pathway. Pain scores remained stable at 3 or less; the number of postdischarge refill requests was unchanged.

IN PRACTICE:

“Our findings suggest that reduction of postoperative opioid dissemination through opioid-free discharge after pancreatectomy and other major cancer operations may be realistic and feasible by following this no-cost blueprint,” the authors concluded. In an accompanying editorial, Melissa Hogg, MD, from NorthShore University Health System in Evanston, Ill., said the “study inspired me to update our institution’s [early recovery after surgery] protocol to reduce and eliminate opioid prescriptions.”
 

SOURCE:

The study was led by Ching-Wei D. Tzeng, MD, of the University of Texas MD Anderson Cancer Center, Houston. It was published online in JAMA Surgery.
 

LIMITATIONS:

The study evaluated the opioid protocol at a single center, which may limit the generalizability of the findings. The researchers did not receive patient feedback on pain control expectations or postoperative quality of life.
 

DISCLOSURES:

Dr. Tzeng reported receiving consultant fees and a sponsored research agreement from PanTher outside the submitted work. Dr. Hogg reported receiving training and travel funds from Intuitive Money. No other disclosures or outside funding were reported.

A version of this article appeared on Medscape.com.

SINGAPORE – Heavily pretreated patients with EGFR-mutated non–small cell lung cancer (NSCLC) may experience a clinically meaningful benefit with the antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd), new phase 2 trial results suggest.

In the trial, almost 30% of patients receiving HER3-DXd achieved an objective response, and patients’ median overall survival approached 1 year.

HER3-DXd has “emerged as a promising therapy” in this patient population, “for whom available treatment options provide only limited efficacy,” concluded lead study author Helena A. Yu, MD, from Memorial Sloan Kettering Cancer Center, New York City, who presented findings from the HERTHENA-Lung01 trial at the 2023 World Conference on Lung Cancer.

The results were simultaneously published in the Journal of Clinical Oncology.

Acquired resistance to therapy among heavily pretreated patients with EGFR-mutated NSCLC is “universal,” Dr. Yu explained. The mechanisms of resistance to first-line osimertinib are also “diverse” and hard to identify. Salvage therapies after failed EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy offer “only a limited and transient and clinical benefit,” she said.

And with limited treatment options available to patients resistant to TKIs, there is a “high unmet medical need” for new therapies, said Helena Linardou, MD, PhD, who was not involved in the study.

HER3-DXd consists of a fully human anti-HER3 immunoglobulin G1 monoclonal antibody (patritumab) attached to a topoisomerase I inhibitor payload (DXd) via a tetrapeptide-based cleavable linker.

HER3, Dr. Linardou explained, is a “biologically and clinically important target” in NSCLC. It is highly expressed in NSCLC, upregulated in TKI-resistant EGFR-mutated NSCLC, and is associated with a poor prognosis.

After promising phase 1 data, Dr. Yu and colleagues conducted a phase 2 trial in patients with advanced EGFR-mutated NSCLC who had progressed on systematic therapy and had received EGFR TKI and platinum-based chemotherapy. Patients could have active or previously treated asymptomatic brain metastases.

Patients were initially randomized either to a fixed-dose arm of HER3-DXd 5.6 mg/kg once every 3 weeks or an uptitration arm with doses escalating from 3.2 mg/kg to 4.8 mg/kg to 6.4 mg/kg over three cycles. However, Dr. Yu noted, enrollment in the uptitration arm closed early based on a “benefit-risk assessment.”

The current findings focus on the 225 patients in the fixed-dose arm.

About half of patients had a history of central nervous system metastasis, and patients had a median of three prior lines of systemic therapy. Most patients (92.9%) had previously received a third-generation EGFR TKI, about 40% had received immunotherapy, and all had received platinum-based chemotherapy.

After a median follow-up of 18.9 months, the confirmed objective response rate with HER3-DXd across the whole patient population was 29.8%. The median duration of response was 6.4 months, median progression-free survival was 5.5 months, and median overall survival was 11.9 months.

The results were virtually identical when looking only at patients who had received a third-generation EGFR TKI versus any EGFR TKI. Response rates were also similar regardless of the driver of EGFR TKI resistance.

Among the 30 patients with measurable brain metastases at baseline, 33.3% had a confirmed objective response to therapy. In this group, the disease control rate was 76.7% and the intracranial duration of response was 8.4 months.

To identify biomarkers of response to HER3-DXd, the team stratified the patients by baseline tumor HER3 membrane H-scores. Dr. Yu and colleagues found no differences in the likelihood of having a complete or partial response, stable disease, or progressive disease based on HER3 expression at study entry.

Looking at the safety of the ADC, only 7.1% of patients experienced a treatment-emergent adverse event associated with treatment discontinuation, but close to half of patients (45.3%) experienced a grade 3 or higher treatment-emergent adverse event. Interstitial lung disease, for instance, occurred in 5.3% of patients, including one patient who died.

The safety profile of HER3-DXd in this population appeared to be consistent with previous reports, Dr. Yu noted.

Overall, the findings suggest that “HER3-DXd provided clinically meaningful and durable efficacy” in patients with advanced EGFR-mutant NSCLC that has progressed after EGFR TKI and platinum-based chemotherapy, Dr. Yu said.

“Efficacy was observed across diverse mechanisms of resistance and across a broad range of pretreatment tumor HER3 expression” and the ADC demonstrated “clinically meaningful intracranial antitumor activity,” she added.

Dr. Linardou agreed that the current results suggest that HER3-DXd was associated with a “meaningful and durable efficacy,” including in patients with intracranial metastases, and she pointed to its “easy dosing schedule” and activity across patient subgroups.

However, she noted that, despite the researchers’ best efforts with the data available, “we don’t have a biomarker of activity,” which is a “general issue with ADCs.”

Still, Dr. Linardou said, “HER3 is now a clinically actionable therapeutic target, and this is a great bonus.”

The study was sponsored by Daiichi Sankyo. Dr. Yu declared relationships with AstraZeneca, Daiichi Sankyo, Blueprint Medicines, Janssen, C4 Therapeutics, Cullinan Oncology, Black Diamond Therapeutics, Taiho Oncology, and others. Other authors declare numerous relationships.

A version of this article first appeared on Medscape.com.

SINGAPORE – Heavily pretreated patients with EGFR-mutated non–small cell lung cancer (NSCLC) may experience a clinically meaningful benefit with the antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd), new phase 2 trial results suggest.

In the trial, almost 30% of patients receiving HER3-DXd achieved an objective response, and patients’ median overall survival approached 1 year.

HER3-DXd has “emerged as a promising therapy” in this patient population, “for whom available treatment options provide only limited efficacy,” concluded lead study author Helena A. Yu, MD, from Memorial Sloan Kettering Cancer Center, New York City, who presented findings from the HERTHENA-Lung01 trial at the 2023 World Conference on Lung Cancer.

The results were simultaneously published in the Journal of Clinical Oncology.

Acquired resistance to therapy among heavily pretreated patients with EGFR-mutated NSCLC is “universal,” Dr. Yu explained. The mechanisms of resistance to first-line osimertinib are also “diverse” and hard to identify. Salvage therapies after failed EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy offer “only a limited and transient and clinical benefit,” she said.

And with limited treatment options available to patients resistant to TKIs, there is a “high unmet medical need” for new therapies, said Helena Linardou, MD, PhD, who was not involved in the study.

HER3-DXd consists of a fully human anti-HER3 immunoglobulin G1 monoclonal antibody (patritumab) attached to a topoisomerase I inhibitor payload (DXd) via a tetrapeptide-based cleavable linker.

HER3, Dr. Linardou explained, is a “biologically and clinically important target” in NSCLC. It is highly expressed in NSCLC, upregulated in TKI-resistant EGFR-mutated NSCLC, and is associated with a poor prognosis.

After promising phase 1 data, Dr. Yu and colleagues conducted a phase 2 trial in patients with advanced EGFR-mutated NSCLC who had progressed on systematic therapy and had received EGFR TKI and platinum-based chemotherapy. Patients could have active or previously treated asymptomatic brain metastases.

Patients were initially randomized either to a fixed-dose arm of HER3-DXd 5.6 mg/kg once every 3 weeks or an uptitration arm with doses escalating from 3.2 mg/kg to 4.8 mg/kg to 6.4 mg/kg over three cycles. However, Dr. Yu noted, enrollment in the uptitration arm closed early based on a “benefit-risk assessment.”

The current findings focus on the 225 patients in the fixed-dose arm.

About half of patients had a history of central nervous system metastasis, and patients had a median of three prior lines of systemic therapy. Most patients (92.9%) had previously received a third-generation EGFR TKI, about 40% had received immunotherapy, and all had received platinum-based chemotherapy.

After a median follow-up of 18.9 months, the confirmed objective response rate with HER3-DXd across the whole patient population was 29.8%. The median duration of response was 6.4 months, median progression-free survival was 5.5 months, and median overall survival was 11.9 months.

The results were virtually identical when looking only at patients who had received a third-generation EGFR TKI versus any EGFR TKI. Response rates were also similar regardless of the driver of EGFR TKI resistance.

Among the 30 patients with measurable brain metastases at baseline, 33.3% had a confirmed objective response to therapy. In this group, the disease control rate was 76.7% and the intracranial duration of response was 8.4 months.

To identify biomarkers of response to HER3-DXd, the team stratified the patients by baseline tumor HER3 membrane H-scores. Dr. Yu and colleagues found no differences in the likelihood of having a complete or partial response, stable disease, or progressive disease based on HER3 expression at study entry.

Looking at the safety of the ADC, only 7.1% of patients experienced a treatment-emergent adverse event associated with treatment discontinuation, but close to half of patients (45.3%) experienced a grade 3 or higher treatment-emergent adverse event. Interstitial lung disease, for instance, occurred in 5.3% of patients, including one patient who died.

The safety profile of HER3-DXd in this population appeared to be consistent with previous reports, Dr. Yu noted.

Overall, the findings suggest that “HER3-DXd provided clinically meaningful and durable efficacy” in patients with advanced EGFR-mutant NSCLC that has progressed after EGFR TKI and platinum-based chemotherapy, Dr. Yu said.

“Efficacy was observed across diverse mechanisms of resistance and across a broad range of pretreatment tumor HER3 expression” and the ADC demonstrated “clinically meaningful intracranial antitumor activity,” she added.

Dr. Linardou agreed that the current results suggest that HER3-DXd was associated with a “meaningful and durable efficacy,” including in patients with intracranial metastases, and she pointed to its “easy dosing schedule” and activity across patient subgroups.

However, she noted that, despite the researchers’ best efforts with the data available, “we don’t have a biomarker of activity,” which is a “general issue with ADCs.”

Still, Dr. Linardou said, “HER3 is now a clinically actionable therapeutic target, and this is a great bonus.”

The study was sponsored by Daiichi Sankyo. Dr. Yu declared relationships with AstraZeneca, Daiichi Sankyo, Blueprint Medicines, Janssen, C4 Therapeutics, Cullinan Oncology, Black Diamond Therapeutics, Taiho Oncology, and others. Other authors declare numerous relationships.

A version of this article first appeared on Medscape.com.

SINGAPORE – Heavily pretreated patients with EGFR-mutated non–small cell lung cancer (NSCLC) may experience a clinically meaningful benefit with the antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd), new phase 2 trial results suggest.

In the trial, almost 30% of patients receiving HER3-DXd achieved an objective response, and patients’ median overall survival approached 1 year.

HER3-DXd has “emerged as a promising therapy” in this patient population, “for whom available treatment options provide only limited efficacy,” concluded lead study author Helena A. Yu, MD, from Memorial Sloan Kettering Cancer Center, New York City, who presented findings from the HERTHENA-Lung01 trial at the 2023 World Conference on Lung Cancer.

The results were simultaneously published in the Journal of Clinical Oncology.

Acquired resistance to therapy among heavily pretreated patients with EGFR-mutated NSCLC is “universal,” Dr. Yu explained. The mechanisms of resistance to first-line osimertinib are also “diverse” and hard to identify. Salvage therapies after failed EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy offer “only a limited and transient and clinical benefit,” she said.

And with limited treatment options available to patients resistant to TKIs, there is a “high unmet medical need” for new therapies, said Helena Linardou, MD, PhD, who was not involved in the study.

HER3-DXd consists of a fully human anti-HER3 immunoglobulin G1 monoclonal antibody (patritumab) attached to a topoisomerase I inhibitor payload (DXd) via a tetrapeptide-based cleavable linker.

HER3, Dr. Linardou explained, is a “biologically and clinically important target” in NSCLC. It is highly expressed in NSCLC, upregulated in TKI-resistant EGFR-mutated NSCLC, and is associated with a poor prognosis.

After promising phase 1 data, Dr. Yu and colleagues conducted a phase 2 trial in patients with advanced EGFR-mutated NSCLC who had progressed on systematic therapy and had received EGFR TKI and platinum-based chemotherapy. Patients could have active or previously treated asymptomatic brain metastases.

Patients were initially randomized either to a fixed-dose arm of HER3-DXd 5.6 mg/kg once every 3 weeks or an uptitration arm with doses escalating from 3.2 mg/kg to 4.8 mg/kg to 6.4 mg/kg over three cycles. However, Dr. Yu noted, enrollment in the uptitration arm closed early based on a “benefit-risk assessment.”

The current findings focus on the 225 patients in the fixed-dose arm.

About half of patients had a history of central nervous system metastasis, and patients had a median of three prior lines of systemic therapy. Most patients (92.9%) had previously received a third-generation EGFR TKI, about 40% had received immunotherapy, and all had received platinum-based chemotherapy.

After a median follow-up of 18.9 months, the confirmed objective response rate with HER3-DXd across the whole patient population was 29.8%. The median duration of response was 6.4 months, median progression-free survival was 5.5 months, and median overall survival was 11.9 months.

The results were virtually identical when looking only at patients who had received a third-generation EGFR TKI versus any EGFR TKI. Response rates were also similar regardless of the driver of EGFR TKI resistance.

Among the 30 patients with measurable brain metastases at baseline, 33.3% had a confirmed objective response to therapy. In this group, the disease control rate was 76.7% and the intracranial duration of response was 8.4 months.

To identify biomarkers of response to HER3-DXd, the team stratified the patients by baseline tumor HER3 membrane H-scores. Dr. Yu and colleagues found no differences in the likelihood of having a complete or partial response, stable disease, or progressive disease based on HER3 expression at study entry.

Looking at the safety of the ADC, only 7.1% of patients experienced a treatment-emergent adverse event associated with treatment discontinuation, but close to half of patients (45.3%) experienced a grade 3 or higher treatment-emergent adverse event. Interstitial lung disease, for instance, occurred in 5.3% of patients, including one patient who died.

The safety profile of HER3-DXd in this population appeared to be consistent with previous reports, Dr. Yu noted.

Overall, the findings suggest that “HER3-DXd provided clinically meaningful and durable efficacy” in patients with advanced EGFR-mutant NSCLC that has progressed after EGFR TKI and platinum-based chemotherapy, Dr. Yu said.

“Efficacy was observed across diverse mechanisms of resistance and across a broad range of pretreatment tumor HER3 expression” and the ADC demonstrated “clinically meaningful intracranial antitumor activity,” she added.

Dr. Linardou agreed that the current results suggest that HER3-DXd was associated with a “meaningful and durable efficacy,” including in patients with intracranial metastases, and she pointed to its “easy dosing schedule” and activity across patient subgroups.

However, she noted that, despite the researchers’ best efforts with the data available, “we don’t have a biomarker of activity,” which is a “general issue with ADCs.”

Still, Dr. Linardou said, “HER3 is now a clinically actionable therapeutic target, and this is a great bonus.”

The study was sponsored by Daiichi Sankyo. Dr. Yu declared relationships with AstraZeneca, Daiichi Sankyo, Blueprint Medicines, Janssen, C4 Therapeutics, Cullinan Oncology, Black Diamond Therapeutics, Taiho Oncology, and others. Other authors declare numerous relationships.

A version of this article first appeared on Medscape.com.